WorldWideScience

Sample records for narcotics designer drugs

  1. Narcotic Drug and Marihuana Controls.

    Science.gov (United States)

    Miller, Donald E.

    As a background paper for the National Association of Student Personnel Administrators Drug Education Conference held in November, 1966, this paper focuses first on narcotic control in general, and second, on the reasons for insisting on marijuana control. Brief descriptions are given of the currently existing narcotics acts at federal and state…

  2. Narcotics

    Science.gov (United States)

    ... of well-being by reducing tension, anxiety, and aggression. These effects are helpful in a therapeutic setting but contribute to the drugs ’ abuse. Narcotic/opioid use comes with a variety of ...

  3. 76 FR 5858 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-02-02

    ... ORGANIZATION/DRUG TRAFFICKING ORGANIZATION (a.k.a. ``JOUMAA MLO/DTO''); Beirut, Lebanon; Maicao, Colombia... Investigation, the Administrator of the Drug Enforcement Administration, the Secretary of Defense, the Secretary... support of, the international narcotics trafficking activities of a person designated pursuant to the...

  4. 15 CFR 265.37 - Narcotics and other drugs.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Narcotics and other drugs. 265.37... other drugs. The possession, sale, consumption, or use on the site of narcotic or other drugs illegal... with respect to the possession, sale, consumption, or use of narcotic or other drugs. ...

  5. 19 CFR 162.66 - Penalties for unlading narcotic drugs or marihuana without a permit.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Penalties for unlading narcotic drugs or marihuana... Substances, Narcotics, and Marihuana § 162.66 Penalties for unlading narcotic drugs or marihuana without a permit. In every case where a narcotic drug or marihuana is unladen without a permit, the penalties...

  6. Skin Permeation Enhancers and their Effects on Narcotic Transdermal Drug Delivery Systems through Response Surface Experimental Design

    Directory of Open Access Journals (Sweden)

    A. Moghimi

    2014-02-01

    Full Text Available Drug delivery through skin is often obstructed by low permeability of skin towards most drugs; however, such problem would be solved by application of skin penetration enhancers in the formulations. In the present study, a drug in adhesive patch with buprenorphine as active ingredient was prepared. Drug-in-adhesive transdermal drug delivery systems with different chemical penetration enhancers were designed. For this purpose a response-surface experimental design was used. Response surface methodology based on a three-level, three-variable Box–Behnken design was used to evaluate the interactive effects of dependent variables such as: the rate of skin permeation and adhesion properties including peel strength and tack value. The parameters such as drug release and adhesion were used as independent variables. Levulinic acid, lauryl alcohol and Tween 80 were used as penetration enhancers. In order to prepare samples, buprenorphine with constant concentration was incorporated into acrylic pressure sensitive adhesive with carboxylic functionality and this mixture was added to chemical penetration enhancer with different concentrations. The results show that the cumulative amount of drug release in presence of Tween 80 is 462.9 ± 0.006 μg so it is higher than cumulative amount of drug release in presence of levulinic acid (357.9 ± 0.005 μg and lauryl alcohol (269.5 ± 0.001 μg. Results of adhesion properties such as peel strength and tack reveal that using levulinic acid and lauryl alcohol will increase peel strength while Tween 80 will decrease it. Besides, the results show that all these permeation enhancers have increased tack values.

  7. 78 FR 5562 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-01-25

    ... FLORES, Fausto Isidro). 4. MEZA FLORES DRUG TRAFFICKING ORGANIZATION, Mexico [SDNTK]. Dated: January 17... Director of the Federal Bureau of Investigation, the Administrator of the Drug Enforcement Administration... providing goods or services in support of, the international narcotics trafficking activities of a person...

  8. Legal Position of School Personnel -- Drugs and Narcotics.

    Science.gov (United States)

    Shannon, Thomas A.

    California educators have been given broad discretionary powers to control students who misuse drugs or narcotics, and to develop drug education programs. This paper outlines and discusses legislation dealing with disciplinary actions against drug offenders, and delineates school responsibilities for developing and implementing effective drug…

  9. Translations on Narcotics and Dangerous Drug No. 285

    Science.gov (United States)

    1977-02-17

    the odd exception, but in general the police seem to have a pretty sensible attitude towards addictive narcotics at least. I never hear any... Ciudad Universitaria. Guzman Maldonado said that he has been involved in drug traffic since 1967 when he entered Prepara- tory School No. 5 in Coapa

  10. 19 CFR 162.65 - Penalties for failure to manifest narcotic drugs or marihuana.

    Science.gov (United States)

    2010-04-01

    ... or marihuana. 162.65 Section 162.65 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF... Substances, Narcotics, and Marihuana § 162.65 Penalties for failure to manifest narcotic drugs or marihuana. (a) Cargo or baggage containing unmanifested narcotic drugs or marihuana. When a package of regular...

  11. Translations on Narcotics and Dangerous Drugs, Number 288

    Science.gov (United States)

    1977-03-10

    activities, especially the scope of their drug sales and distribution activities. The Interpol agents also confiscated two pickup trucks, one Izuzu l...Barnett Va- lenzuela, and Eduardo Esquer Alvarado, 35-years old, resident of 79 Educacion Street of this city. Barnett Valenzuela owns the drugs and... especially of the urban lower classes, of a broad and concrete discussion on the problems of the use and abuse of alco- hol, hallucinogens and narcotics

  12. 14 CFR 91.19 - Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marihuana, and... OPERATING AND FLIGHT RULES General § 91.19 Carriage of narcotic drugs, marihuana, and depressant or... operate a civil aircraft within the United States with knowledge that narcotic drugs, marihuana, and...

  13. Translations on Narcotics and Dangerous Drugs, Number 291

    Science.gov (United States)

    1977-03-23

    northern region down to Bangkok as can be seen by the decrease in narcotics prices in parts of the country like Chiang Mai . We must praise the Border...the deputy rector of Chiang Mai University. I think that this project will proceed without any difficulty. CSO: 5300 17 THAILAND UNIVERSITY...ANTINARCOTICS CENTER--A new antinarcotics centre has been set up in Chiang Mai to deal with the suppression of drug trafficking in the north, the

  14. 78 FR 9997 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-02-12

    ... the President to impose sanctions against significant foreign narcotics traffickers and their... controlled by significant foreign narcotics traffickers as identified by the President. In addition, the..., Rio Grande, Zacatecas 98400, Mexico; Matamoros, Tamaulipas, Mexico; Rio Grande, Zacatecas, Mexico; DOB...

  15. 14 CFR 121.15 - Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances. 121.15 Section 121.15 Aeronautics and Space FEDERAL AVIATION....15 Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances. If a...

  16. 14 CFR 133.14 - Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances. 133.14 Section 133.14 Aeronautics and Space FEDERAL AVIATION... narcotic drugs, marihuana, and depressant or stimulant drugs or substances. If the holder of a certificate...

  17. 14 CFR 141.18 - Carriage of narcotic drugs, marijuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marijuana, and depressant or stimulant drugs or substances. 141.18 Section 141.18 Aeronautics and Space FEDERAL AVIATION... General § 141.18 Carriage of narcotic drugs, marijuana, and depressant or stimulant drugs or substances...

  18. 31 CFR 598.309 - Narcotic drug; controlled substance; listed chemical.

    Science.gov (United States)

    2010-07-01

    ...; listed chemical. 598.309 Section 598.309 Money and Finance: Treasury Regulations Relating to Money and... SANCTIONS REGULATIONS General Definitions § 598.309 Narcotic drug; controlled substance; listed chemical. The terms narcotic drug, controlled substance, and listed chemical have the meanings given those terms...

  19. Recent advances in immunosensor for narcotic drug detection

    Science.gov (United States)

    Gandhi, Sonu; Suman, Pankaj; Kumar, Ashok; Sharma, Prince; Capalash, Neena; Suri, C. Raman

    2015-01-01

    Introduction: Immunosensor for illicit drugs have gained immense interest and have found several applications for drug abuse monitoring. This technology has offered a low cost detection of narcotics; thereby, providing a confirmatory platform to compliment the existing analytical methods. Methods: In this minireview, we define the basic concept of transducer for immunosensor development that utilizes antibodies and low molecular mass hapten (opiate) molecules. Results: This article emphasizes on recent advances in immunoanalytical techniques for monitoring of opiate drugs. Our results demonstrate that high quality antibodies can be used for immunosensor development against target analyte with greater sensitivity, specificity and precision than other available analytical methods. Conclusion: In this review we highlight the fundamentals of different transducer technologies and its applications for immunosensor development currently being developed in our laboratory using rapid screening via immunochromatographic kit, label free optical detection via enzyme, fluorescence, gold nanoparticles and carbon nanotubes based immunosensing for sensitive and specific monitoring of opiates. PMID:26929925

  20. Fast analysis of narcotic drugs by optical chemical imaging

    International Nuclear Information System (INIS)

    Fisher, Michal; Bulatov, Vallery; Schechter, Israel

    2003-01-01

    A new technique is proposed for fast detection, identification and imaging of narcotic drugs in their solid phase. This technique, which requires only a tiny sample of a few microns, is based on microscopic chemical imaging. Minor sample preparation is required, and results are obtained within seconds. As far as we know, this is the most sensitive detection system available today for solid drugs. The technique can be applied for fast analysis of minute drug residues, and therefore is of considerable importance for forensic applications. It is shown that identification of drug traces in realistic matrixes is possible. Two main methods were applied in this study for detection of drugs and drug derivatives. The first method was based on direct detection and chemical imaging of the auto-fluorescence of the analyzed drugs. This method is applicable when the analyzed drug emits fluorescence under the experiment conditions, such as lysergic acid diethylamide (known as LSD). The second method was used for obtaining chemical imaging of drugs that do not fluoresce under the experiment conditions. In these cases fluorescent labeling dyes were applied to the examined samples (including the drug and the matrix). Both methods are simple and rapid, and require minor or no sample preparation at all. Detection limits are very low in the picogram range

  1. 14 CFR 125.39 - Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances. 125.39 Section 125.39 Aeronautics and Space FEDERAL AVIATION... AIRCRAFT Certification Rules and Miscellaneous Requirements § 125.39 Carriage of narcotic drugs, marihuana...

  2. 14 CFR 135.41 - Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances. 135.41 Section 135.41 Aeronautics and Space FEDERAL AVIATION... PERSONS ON BOARD SUCH AIRCRAFT General § 135.41 Carriage of narcotic drugs, marihuana, and depressant or...

  3. Terrorism and Drug Trafficking: Technologies for Detecting Explosives and Narcotics

    Science.gov (United States)

    1996-09-01

    The General Accounting Office (GAO) examined information on explosives and narcotics detection technologies that are available or under development. This report discusses (1) funding for those technologies, (2) characteristics and limitations of avai...

  4. 78 FR 70630 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-11-26

    ... providing goods or services in support of, the international narcotics trafficking activities of a person... fax-on-demand service at (202) 622-0077. Background The Kingpin Act became law on December 3, 1999..., Zacatecas, Mexico; nationality Mexico; Tax ID No. 06796108238 (Mexico); C.U.R.P. LOHM611211HZSZRG11 (Mexico...

  5. 77 FR 74915 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-12-18

    .... jurisdiction, owned or controlled by significant foreign narcotics traffickers as identified by the President... Enrique; DOB 25 Mar 1980; POB Culiacan, Sinaloa, Mexico; C.U.R.P. EUEJ800325HSLSSR02 (Mexico) (individual... GUTIERREZ, Julio Cesar, Calle Platon 268, Col. Paso Blanco, Ocotlan, Jalisco, Mexico; DOB 03 Oct 1981; POB...

  6. 78 FR 62946 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-10-22

    ... significant foreign narcotics traffickers as identified by the President. In addition, the Secretary of the...; R.F.C. PAPA751109870 (Mexico); C.U.R.P. PAPA751109HNEDSL04 (Mexico) (individual) [SDNTK] (Linked To... No. 279, Supermanzana 50, Manzana 14, Lote 17, Residencial San Angel, Cancun, Quintana Roo, Mexico...

  7. 77 FR 71480 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-11-30

    ... controlled by significant foreign narcotics traffickers as identified by the President. In addition, the... IBARRA, Mayela), Calle Lago de La Doga 5312, Tijuana, Baja California, Mexico; DOB 24 Feb 1961; POB Coahuila, Mexico; Passport 99020046985 (Mexico); R.F.C. CAIM610224 (Mexico) (individual) [SDNTK]. 2...

  8. 78 FR 47828 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-08-06

    ... significant foreign narcotics traffickers as identified by the President. In addition, the Secretary of the..., Colonia Centro, Culiacan, Sinaloa 80000, Mexico; DOB 21 Dec 1941; POB Sinaloa, Mexico; nationality Mexico; citizen Mexico; R.F.C. NUBA411221867 (Mexico); C.U.R.P. NUBA411221HSLXDN05 (Mexico) (individual) [SDNTK...

  9. 76 FR 58562 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-09-21

    ... controlled by significant foreign narcotics traffickers as identified by the President. In addition, the..., Jalisco, Mexico; Plaza Del Sol Local 28, Zona R, Guadalajara, Jalisco, Mexico; Paseo Del Heliotropo 3426, Monraz, Guadalajara, Jalisco, Mexico; DOB 09 Aug 1955; POB Jalisco, Mexico; Citizen Mexico; Nationality...

  10. 77 FR 63418 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-10-16

    ... significant foreign narcotics traffickers as identified by the President. In addition, the Secretary of the..., Zapopan, Jalisco C.P. 45238, Mexico; Cancun, Quintana Roo, Mexico; R.F.C. SRC-080222-274 (Mexico) [SDNTK..., Guadalajara, Jalisco C.P. 44130, Mexico; R.F.C. UNI-031118-2I6 (Mexico) [SDNTK]. In addition, OFAC is...

  11. 77 FR 14592 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-03-12

    ... controlled by significant foreign narcotics traffickers as identified by the President. In addition, the...''), DOB 13 Aug 1961; POB Culiacan, Sinaloa, Mexico; citizen Mexico; nationality Mexico; C.U.R.P. ZAGJ610813HSLMRS05 (Mexico) (individual) [SDNTK] Entities 2. ZARKA DE MEXICO S.A. DE C.V., Miguel Hidalgo No. 348 Pte...

  12. 75 FR 64781 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-10-20

    ... framework for the President to impose sanctions against significant foreign narcotics traffickers and their...., Martin L. Guzman 259-3, Colonia Villa de Cortes, Delegacion Benito Juarez, Mexico City, Mexico; Folio Mercantil No. 325909 (Mexico); (ENTITY) [BPI-SDNTK] 2. TATES DESARROLLO, S.A. DE C.V., Mexico City, Mexico...

  13. 78 FR 53191 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-08-28

    ... significant foreign narcotics traffickers as identified by the President. In addition, the Secretary of the...) of the Kingpin Act. 1. PARRA SANCHEZ, Mario; DOB 11 Nov 1970; POB Culiacan, Sinaloa, Mexico; C.U.R.P. PASM701111HSLRNR07 (Mexico) (individual) [SDNTK] (Linked To: BUENOS AIRES SERVICIOS, S.A. DE C.V.; Linked To...

  14. 14 CFR 137.23 - Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances. 137.23 Section 137.23 Aeronautics and Space FEDERAL AVIATION... drugs, marihuana, and depressant or stimulant drugs or substances. If the holder of a certificate issued...

  15. ACUTE NARCOTIC DRUG INTOXICATIONS: ETIOLOGY, SEX/AGE DISTRIBUTION AND CLINICAL OUTCOME

    Directory of Open Access Journals (Sweden)

    Petko Marinov

    2017-01-01

    Full Text Available Purpose: Poisoning with drugs is a serious medical and social problem worldwide. Retrospective analysis of acute poisoning with narcotic drugs had been performed in Varna region for 25 years (1991-2015. Material and Methods: The number of patients received hospital treatment after poisonings with narcotic substances was 677, which represented 3.9% of all acute exogenous intoxications. Results: Narcotic poisonings were more common in men – 546 (80.6%, than in women – 131 (19.4 %. The ratio male/ female was 4.17:1. The largest number of intoxications were in the age group up to 24 years – 1123 (66%, and only 2.65% of patients were over 45 years. Death was registered in 6 (0.9% patients.

  16. Frequency of neonatal abstinence syndrome (NAS and type of the narcotic substance in neonates born from drug addicted mothers

    Directory of Open Access Journals (Sweden)

    Fatemeh Nayeri

    2015-02-01

    Full Text Available Abstract Background and objective: NAS is a combination of signs and symptoms that due to physical and mental dependency, develops in neonates born from drug addicted mothers. The onset of NAS varies in accordance with the type, amount, frequency and duration of substance used. Because of diverse and unclear pattern of substance abuse in Iranian addicted pregnant mothers in comparison with western countries, this multi-center study has been designed to evaluate NAS in neonates born from drug addicted mothers. Material and method: A cross sectional study was carried out on newborns of narcotic addicted mothers during the first six months of 2008. The newborn’s status and clinical signs were checked by physical examination and scored by the Finnegan scoring system. Results: In this study 100 neonates born from narcotic addicted mothers were examined; the most used narcotic was crack (36%. 60% of neonates showed signs of NAS. The most prevalent signs of NAS were increased muscle tonicity (60%/7, irritability (59%/6 and increased moro reflex (51%/8. Neonates born from crack abusers, in comparison with other drugs, were significantly at risk of NAS (100% vs.87%, p

  17. Risk Factors of Narcotic and Psychoactive Drugs Use among University and High School Student

    Directory of Open Access Journals (Sweden)

    Ali Kashi

    2010-05-01

    Full Text Available Aim: Today use of different banned substances such as narcotic, psychoactive and energetic drugs are social problem that has created worry in different levels of human societies. The aim of present study was examined the prevalence of use of narcotic and psychoactive drugs among high school and university students also identifying of risk factors associated with the use of this materials. Method: The population of this descriptive survey study was all students of high school and university of Khodabandeh city. By cluster random sampling 580 students of high school and university selected and questionnaires distributed among them. After eliminating incomplete questionnaires 480 students remained as research sample. Results: In consideration of selected sample the most important reasons of using of narcotics are: enjoying and curiosity, exposed to bad environment like addicted friends and families, joblessness, economic problems, lack of information and loss of affection. Conclusion: The analysis of the results indicated the high prevalence of narcotic and drugs use and necessity of codification of preventive programs for these people.

  18. The IHO as Actor The case of cannabis and the Single Convention on Narcotic Drugs 1961

    Directory of Open Access Journals (Sweden)

    James H. Mills

    2016-12-01

    Full Text Available After the Second World War the United Nations (UN assumed the role of the League of Nations in formulating and operating the international regulatory framework for narcotic drugs. It gathered masses of information from across countries and continents while acting as both a forum and an agent for the emergence of agreed approaches to a heterodox array of substances. This article will examine the story of the inclusion of cannabis in the 1961 Single Convention on Narcotic Drugs. It will argue that in the years after 1945, it was officials at the UN and the WHO that played crucial roles in shaping opinions of the drug and in securing its place in the Convention.

  19. 78 FR 42589 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-07-16

    ... Intelligence Agency, the Director of the Federal Bureau of Investigation, the Administrator of the Drug..., Israel; Commercial Registry Number 513174466 (Israel) [SDNTK]. Dated: July 9, 2013. Adam J. Szubin...

  20. 76 FR 58562 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-09-21

    ... worldwide basis with the objective of denying their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin... Intelligence Agency, the Director of the Federal Bureau of Investigation, the Administrator of the Drug...

  1. 77 FR 69706 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-11-20

    ... on a worldwide basis, with the objective of denying their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The... Intelligence Agency, the Director of the Federal Bureau of Investigation, the Administrator of the Drug...

  2. Translations on Narcotics and Dangerous Drugs, Number 269

    Science.gov (United States)

    1976-10-28

    Combat of Traffickers 64 PANAMA Briefs Drug Trafficker’s Arrest 65 Drug Control Statistics 65 Three From U.S. 65 PERU Briefs State Drug Law 66...in Viru, Peru , was identified as Gabriel Eduardo Romero. The Cali police said that Romero had a record as a drug trafficker and that he is widely...Narino Battalion. Counsel for the defense alleged that Vega Perez suffers from diabetes and will there- by receive better medical treatment. The

  3. Translations on Narcotics and Dangerous Drugs, Number 318

    Science.gov (United States)

    1977-09-08

    cent of those ar- rested for drug offences had no religious back- ground. He therefore called on ’ the Malaysian Inter-Re- , ligions...illicit drugs, it would mean that 15 out of every 1,000 Malaysians have drug- tainted fingers (based on a population figure of 12 mil- lion).. An idea...a certain de- gree of misunderstanding concerning crime and ad-’ diets . Addicts have, been ac- cused of being violent as a result of their drug

  4. Multiplexed detection of metabolites of narcotic drugs from a single latent fingermark.

    Science.gov (United States)

    Hazarika, Pompi; Jickells, Sue M; Wolff, Kim; Russell, David A

    2010-11-15

    An immunoassay based technique is used for the detection of psychoactive substances in the sweat deposited within fingermarks of a narcotic drug user. Magnetic particles functionalized with antimorphine and antibenzoylecgonine antibodies were used for the detection of a metabolite of heroin (morphine) and a metabolite of cocaine (benzoylecgonine), respectively. The drug metabolites were detected individually as well as simultaneously from a single fingermark. The images of the fingermarks obtained using brightfield and fluorescence microscopy were of high evidential quality with resolution to enable identification of an individual in addition to providing information on drug usage.

  5. Translations on Narcotics and Dangerous Drugs No. 271

    Science.gov (United States)

    1976-11-11

    Worth 25,000 Kyats Seized in Rangoon (MYANMA ALIN, 18 Oct 76) 10 Marihuana Burned in Okto (MYANMA ALIN, 2 Oct 76) 11 MALAYSIA American... Marihuana , Cocaine Pushers, Addicts Arrested (EL TIEMPO, 23 Sep 76) 29 Briefs Drug Ring Smashed 31 Drug Hauls and Arrests 31 Drug Traffickers Arrested...lead of the Labor Governments in New South Wales and South Australia in moves to legalise marihuana ," he said. A submission by the Australian

  6. 76 FR 23644 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-04-27

    ... Defense, the Secretary of State, and the Secretary of Homeland Security when designating and blocking the...: (1) Materially assisting in, or providing financial or technological support for or to, or providing...; citizen Turkey; Turkish Identification Number 23860719950 (Turkey) (individual) [SDNTK] 2. KALKAN, Duran...

  7. 77 FR 14859 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-03-13

    ... of State, and the Secretary of Homeland Security when designating and blocking the property and... assisting in, or providing financial or technological support for or to, or providing goods or services in.... BAQBANI, Mohammad Akhusa); DOB 5 Jan 1961; alt. DOB 1947; POB Zabol, Iran; citizen Iran; Islamic...

  8. 78 FR 66105 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-11-04

    ..., the Secretary of Defense, the Secretary of State, and the Secretary of Homeland Security may designate... found to be: (1) Materially assisting in, or providing financial or technological support for or to, or... 1965; POB Madrid, Spain; citizen Spain; alt. citizen Peru; D.N.I. 01927713-Z (Spain); alt. D.N.I...

  9. 75 FR 24773 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-05-05

    ... State, and the Secretary of Homeland Security when designating and blocking the property and interests... in, or providing financial or technological support for or to, or providing goods or services in.... LORENZANA LIMA, Valdemar); La Reforma, Zacapa, Guatemala; DOB 19 Feb 1940; POB Guatemala; Citizen Guatemala...

  10. 78 FR 53007 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-08-27

    ... of State, and the Secretary of Homeland Security may designate and block the property and interests... in, or providing financial or technological support for or to, or providing goods or services in... Zacapa, Guatemala; nationality Guatemala; citizen Guatemala; Cedula No. R-19 42080 (Guatemala); Passport...

  11. 78 FR 8701 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-02-06

    ... Security may designate and block the property and interests in property, subject to U.S. jurisdiction, of persons who are found to be: (1) Materially assisting in, or providing financial or technological support.... ``DIEGO RASTROJO''); DOB 07 Apr 1971; POB Bolivar, Valle de Cauca, Colombia; nationality Colombia; citizen...

  12. 75 FR 27118 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-05-13

    ... of State, and the Secretary of Homeland Security when designating and blocking the property and... assisting in, or providing financial or technological support for or to, or providing goods or services in.../o NEGOCIAMOS MCM LTDA, Bogota, Colombia; DOB 16 Jul 1968; Citizen Colombia; Cedula No. 51921171...

  13. 76 FR 25405 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-05-04

    ... Defense, the Secretary of State, and the Secretary of Homeland Security when designating and blocking the...: (1) Materially assisting in, or providing financial or technological support for or to, or providing...-SHAYESTEH, Guelin, 80331 Muenchen, Bayern, Germany; DOB 15 Feb 1962; citizen Germany (individual) [SDNTK] 3...

  14. 78 FR 28289 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-05-14

    ... Defense, the Secretary of State, and the Secretary of Homeland Security may designate and block the...) Materially assisting in, or providing financial or technological support for or to, or providing goods or... Nov 1974; citizen Mexico (individual) [SDNTK]. 2. LOPEZ AISPURO, Armando; DOB 27 Oct 1969; POB...

  15. 77 FR 22846 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-04-17

    ... of State, and the Secretary of Homeland Security may designate and block the property and interests... in, or providing financial or technological support for or to, or providing goods or services in... Jul 1967; alt. DOB 31 Jul 1968; citizen Guatemala; nationality Guatemala; Identification Number 0-16...

  16. 77 FR 38140 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-06-26

    ..., the Secretary of Defense, the Secretary of State, and the Secretary of Homeland Security may designate... found to be: (1) Materially assisting in, or providing financial or technological support for or to, or...''); DOB 01 Oct 1979; POB Nawzad District of Helmand Province; citizen Afghanistan (individual) [SDNTK]. 3...

  17. 78 FR 53007 - Additional Designation, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-08-27

    ... of State, and the Secretary of Homeland Security may designate and block the property and interests... in, or providing financial or technological support for or to, or providing goods or services in...; citizen Venezuela; Cedula No. 11295239 (Venezuela) (individual) [SDNTK]. Dated: August 21, 2013. Barbara C...

  18. Translations on Narcotics and Dangerous Drugs, Number 287

    Science.gov (United States)

    1977-03-03

    138] CONTENTS (Continued) Page MALAYSIA Briefs 12,800 Drug Offenders Since 1970 11 Drug Traffickers Sentenced to Death 11 Soldier Jailed for...1330 GMT 16 Feb 77 BK] CSO: 5300 10 MALAYSIA BRIEFS 12,800 DRUG OFFENDERS SINCE 1970—Kuala Lumpur, Sun.—About 12,800 people have been arrested...health be captured. 91 "Ester" is dark, obese and of medium height with long, straight hair. She is about 45 years old and has an eye disease

  19. Translations on Narcotics and Dangerous Drugs, Number 311

    Science.gov (United States)

    1977-07-21

    concealing drugs have included both unsophisticated and ingeni- ous methods, such as transport in cans of tomato juice, pickled chiles and even in...Police] of Agua Prieta upset the drug traffickers by seizing a power- ful light plane used to carry marihuana to the United States. Ernesto Avila...Arizona nar- cotics agents. The Stationer II light plane, registration No N7280N, was found abandoned at the Agua Prieta airport. Alfredo Vazquez

  20. Translations on Narcotics and Dangerous Drugs. Number 297

    Science.gov (United States)

    1977-05-03

    investigate the non- medical use of drugs, spent several hours with a mem- ber of the Beatles, his wife and a Toronto music concert promoter and smoked...obsessive feeling of guilt? The drug therapist, like the cancer 69 specialist, customarily fails; for them this is hard because people do not forgive...products throughout the national territory: opium (1.856 kg), morphine (1.266 kg, 34 ampoules), heroin (103.481 kg), cocaine (2.16 kg), cannabis

  1. Translations on Narcotics and Dangerous Drugs, Number 302

    Science.gov (United States)

    1977-06-01

    were aged between 17 and 35. He said that between 1970 and last year, 379 Malaysians were arrested for drug offenses overseas. Datuk Haji Ngah said...drug processing centre at the Malaysian -Thai border. He warned that the country’s development would be affected and the people would suffer if the...Thai actor with three kilogrammes of No 3 heroin and a .38 revolver on Charoen Krung Road near the Capitol cinema . They were identified as Pol Cpl

  2. Translations on Narcotics and Dangerous Drugs No. 298

    Science.gov (United States)

    1977-05-06

    19 Apr 77) 18 Bangkok Court Sentences Four Drug Traffickers (BANGKOK POST, 23 Apr 77) 20 Briefs Chiang Mai Heroin Factory 21 Thailand...BRIEFS CHIANG MAI HEROIN FACTORY— Chiang Mai —Border patrol police seized a heroin factory at Ban Huai Chae, Tambon Muang Kong of Chiang Dao District...drug enforcement officers stationed in Bangkok. [Text] [Bangkok NATION REVIEW in English 25 Apr 77 p 1 BK] TWO HEROIN RAIDS— Chiang Mai —Five men

  3. Translations on Narcotics and Dangerous Drugs, Number 284.

    Science.gov (United States)

    1977-02-10

    they also cultivate the land, so as to find in nature, through work therapy , the release and sublima- tion they sought in drugs. "These 6 months of...The sierra of Sinaloa pro- duces, nevertheless, an amount of money three times greater than the fertile valley of Culiacan, where horticulture has... children of 10 in much the same way as among adults. He said, "Drug addiction in Morelos is under attack by the Secretariats of Public Education /SEP7

  4. Translations on Narcotics and Dangerous Drugs No. 268

    Science.gov (United States)

    1976-10-21

    COSTA RICA INDICTMENT OF DRUG TRAFFICKERS San Jose LA NACION in Spanish 24 Aug 76 pp 10a, 11a PA [Text] Third Arraigning Judge Maria Luisa Castillo has...been distributing drugs in Las Lomas de Chapultepec . The prisoners will today be turned over to the Directorate General of Pre- Trial Investigations...Guerra, Mary Iraida Rengifo Castillo , Zaida Maria Porras de Marcano and Mercedes Teodora Perez Zambrano were arrested on 5 August. Ten jars containing

  5. Translations on Narcotics and Dangerous Drug No. 289.

    Science.gov (United States)

    1977-03-16

    the crime on the morning of 10 February, she guar - antees: "I had never before seen the individuals who killed my husband." She also claims that she...Confiscated goods included 126 kilograms of gum , 101 tons of mari- huana, 26 kilograms of processed drugs and 20 airplanes. Also 693 national drug...represented a value of some DM4 million—DM10-15 million calculated at black market prices. The powder was 5 kg of pure cocaine, of higher quality than

  6. Translations on Narcotics and Dangerous Drugs, Number 299

    Science.gov (United States)

    1977-05-11

    A six-man party led by the deputy OCPD [Officer in Charge of Police Department], acting ASP [Assistant Superintendent of Police] Tang Yau Hie also...just prepared from opium when police moved in. The stoves were still burning and some drugs were recovered from the pans. Kulim OCPD Deputy Supt

  7. Translations on Narcotics and Dangerous Drugs, Number 293.

    Science.gov (United States)

    1977-04-06

    of Koh’s Johore-registered Datsun where the drugs were found after Mr Lim Chye Huat, who was holding a watching brief for Messrs United Keng Soon...prime minister that Article 21 be imposed against two Chinese Haw heroin traffickers, Lin Taisiang and Mrs Ma Chin -muai, who were caught with k.l kgs

  8. Translations on Narcotics and Dangerous Drugs, Number 283

    Science.gov (United States)

    1977-02-03

    Quiroz Carrillo, 20; Virginia Mora Alejo; Elida Alcorta de Torres, wife of Torres Solis, alias "El Pajaro;" Virginia Mora; Alicia and Dora Mora...INMATES-Raul Mendoza Diaz and the director of Federal Health, Dr Fernando Herrera Negrete, will engage in a campaign to detect drug addiction among

  9. Translations on Narcotics and Dangerous Drugs No. 275.

    Science.gov (United States)

    1976-12-09

    8217Vast’ Drug Network (HERALD, 25 Nov 76) l7 CHILE Marihuana Grower, Trafficker Arrested (LA TERCERA DE LA HORA, 10 Nov 76) 18 COLOMBIA...17 CHILE MARIHUANA. GROWER, TRAFFICKER ARRESTED Santiago LA TERCERA DE IA HORA in Spanish 10 Nov 76 p 27 [Text] Between 250,000 and 300,000...mountainous Aguas Negras region in the jurisdiction of Solano, where seven per- sons were arrested and a very complete laboratory was seized, together

  10. Translations on Narcotics and Dangerous Drugs, Number 272

    Science.gov (United States)

    1976-11-18

    including "marihuana" paper, and a stapler. On 18 September. 28 Luis, who said that he was a receptionist at Comodoro Hotel ( Duque de Caxias Avenue...people. Two hours later the five men from Sinaloa were arrested at the Elba Hotel. They were identified as Efrain Zazueta Beltran, Pedro Salazar Ramirez...national ring of drug traffickers known as the "French Connection" entered the state penitentiary today to begin serving their terms. They are: Pedro

  11. Translations on Narcotics and Dangerous Drugs, Number 281.

    Science.gov (United States)

    1977-01-21

    Mr F. Potts, said the State’s industry was of economic and national strategic importance. He said Australia would soon become one of the world’s...have their headquarters in those highly industrialized nations. These statements made by Pedro Ojeda Paullada (currently Secretary of Labor and...involved in the drug traffic. She lives on Tepanco Street, Parque San Andres District, Coyoacan where the marihuana was found. Jovita Ramirez Garcia

  12. Translations on Narcotics and Dangerous Drugs, Number 278

    Science.gov (United States)

    1976-12-30

    Trafficker Arrested k^ MEXICO Addiction Among Mexican Youths Discussed (ismael Mercado Andrews; EL DIA, 31 Oct 76) k6 Police Uncover Heroin Ring...were arrested. These men were released 2 days later at the order of the 2d Municipal Criminal Judge, Dario Leon Perez. This decision has been the...ILUSTRADO) 31 Oct 76 pp 2, 3 [Article by Ismael Mercado Andrews] [Text] Guido Belsasso, director of the Mexican Center for Drug Dependency

  13. Translations on Narcotics and Dangerous Drugs, Number 317

    Science.gov (United States)

    1977-08-31

    the command of Maj Camilo Gomez Bonilla arrested eight persons engaged in the cocaine and cocaine:paste traffic. The persons taken into custody... Pablo Morales Santanice, coordinator of the campaign against drug 117 trafficking in Durango, acknowledged the incident and said that...Dionisio Ocotepec, where a laboratory was destroyed. In the town of San Pablo Guila, another clandestine laboratory was found. And a Ford Maverick car

  14. Translations on Narcotics and Dangerous Drugs, Number 310

    Science.gov (United States)

    1977-07-14

    May 77) 97 NEAR EAST AND NORTH AFRICA Shocking Statistics, Warning to Families (ETTELA’AT, 12 May 77) 100 Cache of Opium Discovered in Oil ...until we could no longer hear the sound of the pickup truck’s engine. Before he left, he said to us: ’Don’t talk too much or we may ’ fry ’ you at...backpacks and food. Once in the area, they pick fruits in the forests: oranges, mangoes, limes, avocados . It is a veritable drug paradise because

  15. Translations on Narcotics and Dangerous Drugs, Number 277

    Science.gov (United States)

    1976-12-23

    information about the true identity of Curtis Rüssel when he was arrested in June of 1975 with two other persons on the banks of the Rio Bravo by...Juarez EL FROWTERIZO in Spanish 19 Oct 76 p 3-A] 8587 HEROIN, MARIHUANA, COCAINE SEIZED--San Luis Rio Colorado, Sonora, l8 Oct. A light plane...Victoria and Rimac districts. [Text] [Lima EL COMERCIO in Spanish 1 Nov 76 p 32] 8143 SEVEN TRAFFICKERS SENTENCED—Seven drug traffickers were

  16. Translations on Narcotics and Dangerous Drugs No. 286.

    Science.gov (United States)

    1977-02-24

    of a powerful drug ring operating in the country. The police will continue investigating. [Quito EL COMERCIO in Spanish 4 Feb 77 p 10 PA...as a result of the police raid. [Lima EL COMERCIO in Spanish 3 Feb 77 p 34 PA] COCAINE-PROCESSING LABORATORY—Arequipa, Peru, 31 Jan—The police have...grinding mills and an unspecified quantity of semi-processed plants. [Lima EL COMERCIO in Spanish 1 Feb 77 p 29 PA] COCAINE PASTE HAUL—Lima, 1 Feb

  17. Terrorism and Drug Trafficking: Responsibilities for Developing Explosives and Narcotics Detection Technologies

    Science.gov (United States)

    1997-04-01

    This report discusses (1) the roles, responsibilities, and authority of : agencies that establish policy, provide funds or oversee funding requests, : and develop explosives and narcotics detection technologies; : (2) mechanisms used to coordinate th...

  18. Transcultural use of narcotic water lilies in ancient Egyptian and Maya drug ritual.

    Science.gov (United States)

    Emboden, W A

    1981-01-01

    Comparisons are made between ancient ritual uses of the flowers of Nymphaea (Nymphaeaceae) in Maya and Egyptian civilizations. Recurrent motifs encountered in the art of both of these ancient civilizations suggests that the role fo the water lily was that of a narcotic (psychodysleptic) used to mediate ecstasis among a priestly caste. Relevant literature is reviewed as are chemical data. Elements in the complex belief systems of these two civilizations need to be reinterpreted in view of the use of two water lilies as ritual narcotics. The species implicated are Nymphaea caerulea Sav., in Egypt, and N. ampla DC., among the Maya.

  19. Using PANDA (Preventing the Abuse of Tobacco, Narcotics, Drugs, and Alcohol) in a Baltimore City Head Start Setting: A Preliminary Study.

    Science.gov (United States)

    Belcher, Harolyn M. E.; Lockhart, Paula J.; Perkins-Parks, Susan; McNally, Margaret

    2000-01-01

    Describes an evaluation of a substance abuse prevention curriculum, Preventing the Abuse of Tobacco, Narcotics, Drugs, and Alcohol (PANDA), taught to African American Head Start preschool students, examining changes in children's self-concept following participation. Overall, students demonstrated significantly improved self-concept, and PANDA…

  20. The concept and tasks of the basic method of investigation of crimes related to illegal trafficking narcotic drugs

    Directory of Open Access Journals (Sweden)

    Chistova L.E.

    2017-04-01

    Full Text Available the article substantiates the need to develop a basic methodology for investigating crimes related to illicit trafficking in narcotic drugs due to the fact that these crimes are inextricably linked, interdependent and can not be carried out separately from each other in principle. The existing separate private methods develop recommendations for the investigation of specific types of crimes, for example, only smuggling of these funds or their sale and they are not connected with each other. In this regard, it is not possible to trace the whole cycle of criminal activity from the introduction of controlled means to illicit trafficking prior to their sale. Therefore, the basic methodology for investigating such crimes will allow us to trace the whole chain of criminal acts and to reveal all the circumstances that affect the full and objective investigation of such crimes.

  1. Studies on effective atomic numbers for photon energy absorption and electron density of some narcotic drugs in the energy range 1 keV-20 MeV

    Science.gov (United States)

    Gounhalli, Shivraj G.; Shantappa, Anil; Hanagodimath, S. M.

    2013-04-01

    Effective atomic numbers for photon energy absorption ZPEA,eff, photon interaction ZPI,eff and for electron density Nel, have been calculated by a direct method in the photon-energy region from 1 keV to 20 MeV for narcotic drugs, such as Heroin (H), Cocaine (CO), Caffeine (CA), Tetrahydrocannabinol (THC), Cannabinol (CBD), Tetrahydrocannabivarin (THCV). The ZPEA,eff, ZPI,eff and Nel values have been found to change with energy and composition of the narcotic drugs. The energy dependence ZPEA,eff, ZPI,eff and Nel is shown graphically. The maximum difference between the values of ZPEA,eff, and ZPI,eff occurs at 30 keV and the significant difference of 2 to 33% for the energy region 5-100 keV for all drugs. The reason for these differences is discussed.

  2. Neglected simultaneous bilateral femoral neck fractures secondary to narcotic drug abuse treated by bilateral one-staged hemiarthroplasty: a case report

    Directory of Open Access Journals (Sweden)

    Vahedi Ehsan

    2010-06-01

    Full Text Available Abstract Simultaneous bilateral femoral neck fractures are extremely rare and associated with various conditions. Up to now Most cases had correlations with major trauma, repetitive minor trauma, seizure, parathyroid or renal dysfunction, anti-epileptic medications, seizure, etc. A 28-year-old addict man referred to us with a 10-year history of narcotic drug abuse and history of 8 months bilateral groin pain. He admitted with displaced bilateral femoral neck fracture. Because of long duration of this condition and osteonecrosis revealed on bone scan, one-staged bilateral hip hemiarthroplasty was done. A good function was noted after surgery to 4-month follow up. Up to now, have not be founded in the literature that a case of bilateral femoral neck fracture associated with narcotic drug abuse. Because of negative effects of opium or smoking on bone tissues, a simple bone pain should aware us about the risk of stress or fatigue fracture.

  3. Effectiveness of Hope Therapy on Reducing Depressive Symptoms and Preventing of Relapse in Cure-Seeker Women with Dependency to Narcotic Drugs

    OpenAIRE

    Akram S Raesian; Mahmood Golzari; Ahmad Borjali

    2011-01-01

    Introduction: The aim of the present research was the investigation of the effectiveness of hope therapy on reduction of the degree of depression symptoms and prevention of relapse in cure-seeker women with dependency to narcotic drugs. Method: In semi-experimental research method 20 clients who diagnosed as substance abuse disorder that completed detoxification period successfully, and they were scored more than 14 in depression symptoms (Beck depression questionnaire, second edition) select...

  4. Calculation of absorption parameters for selected narcotic drugs in the energy range from 1 keV to 100 GeV

    Science.gov (United States)

    Akman, Ferdi; Kaçal, Mustafa Recep; Akdemir, Fatma; Araz, Aslı; Turhan, Mehmet Fatih; Durak, Rıdvan

    2017-04-01

    The total mass attenuation coefficients (μ/ρ), total molecular (σt,m), atomic (σt,a) and electronic (σt,e) cross sections, effective atomic numbers (Zeff) and electron density (NE) were computed in the wide energy region from 1 keV to 100 GeV for the selected narcotic drugs such as morphine, heroin, cocaine, ecstasy and cannabis. The changes of μ/ρ, σt,m, σt,a, σt,e, Zeff and NE with photon energy for total photon interaction shows the dominance of different interaction process in different energy regions. The variations of μ/ρ, σt,m, σt,a, σt,e, Zeff and NE depend on the atom number, photon energy and chemical composition of narcotic drugs. Also, these parameters change with number of elements, the range of atomic numbers in narcotic drugs and total molecular weight. These data can be useful in the field of forensic sciences and medical diagnostic.

  5. Innovations: Alcohol & drug abuse: Narcotics on the net: the availability of Web sites selling controlled substances.

    Science.gov (United States)

    Forman, Robert F

    2006-01-01

    The Internet is not only a vital medium for communication, entertainment, and commerce, but it is also an outlet for illicit drug sales. Although the U.S. Controlled Substances Act regulates access to certain drugs by requiring prescriptions, unique characteristics of the Internet create significant challenges for the enforcement of U.S. drug policies. In the late 1990s "no prescription Web sites" (NPWs) began to emerge, which allow persons to purchase drugs, such as opiates, without a prescription. Given the likely role of NPWs in increasing prescription drug abuse, health care professionals must develop and disseminate strategies for helping patients who are affected by these Web sites.

  6. [Designer drugs in Jutland].

    Science.gov (United States)

    Simonsen, K W; Kaa, E

    2001-04-16

    The aim of this investigation was to examine illegal tablets and capsules seized in Jutland, the western part of Denmark, during the period 1995-1999. The drugs are described according to technical appearance (colour, logo, score, diameter) and content of synthetic drugs. All illegal tablets and capsules received during the period 1995-1999 (109 cases containing 192 different samples) were examined. MDMA was the most common drug and was seen during the entire period. Amphetamine was the second most common drug and has been frequently detected during the the last two years. Drugs like MDE, MBDB, BDB, and 2-CB were rarely seen and they disappeared quickly from the illegal market. MDA appeared on the market at the end of 1999. Only 53% of the tablets contained MDMA as the sole drug. Eighty-one percent of the tablets/capsules contained only one synthetic drug, whereas 13% contained a mixture of two or more synthetic drugs. Six per cent of the samples did not contain a euphoric drug/designer drug. The content of MDMA, MDE, and amphetamine in the tablets varied greatly. MDMA is apparently the drug preferred by the users, but still only half of the tablets contained MDMA as the only drug. The rest of the tablets contained either another synthetic drug or a mixture of drugs. In conclusion, the increasing supply of various drugs with different and unpredictable effects and of miscellaneous quality brings about the risk of serious and complicated intoxications.

  7. Drug Take Back in Hawai‘i: Partnership Between the University of Hawai‘i Hilo College of Pharmacy and the Narcotics Enforcement Division

    Science.gov (United States)

    Batz, Forrest; Juarez, Deborah Taira; Ladao, Lani C

    2014-01-01

    Unused/unwanted medications in households and patient care facilities expose vulnerable populations, including children, elders, and pets, to potential harm through inadvertent ingestion, as well as the potential for theft and assault. Hawai‘i Administrative Rules prohibit the return of any prescription medications to retail pharmacies after dispensing. The Hawai‘i Narcotics Enforcement Division (NED) partnered with the University of Hawai‘i at Hilo Daniel K. Inouye College of Pharmacy (CoP) in eleven Drug Take Back events throughout the state. Most participants heard of the events via newspaper and television marketing. The most common methods of medication disposal are via trash or down household drains. Over 8,000 lbs of unused/unwanted medications was collected, identified and logged from 2011 through 2012. The majority of returned drugs were non-controlled substances (90%). Commonly returned medications included prescription cardiac medications such as simvastatin and lisinopril, non-prescription analgesics such as aspirin and ibuprofen, and dietary supplements such as vitamins and iron. Commonly returned controlled substance medications included narcotics such as hydrocodone/acetaminophen combinations and oxycodone, and sedative hypnotics such as zolpidem and lorazepam. PMID:24470984

  8. Drug take back in Hawai'i: partnership between the University of Hawai'i Hilo College of Pharmacy and the Narcotics Enforcement Division.

    Science.gov (United States)

    Ma, Carolyn S; Batz, Forrest; Juarez, Deborah Taira; Ladao, Lani C

    2014-01-01

    Unused/unwanted medications in households and patient care facilities expose vulnerable populations, including children, elders, and pets, to potential harm through inadvertent ingestion, as well as the potential for theft and assault. Hawai'i Administrative Rules prohibit the return of any prescription medications to retail pharmacies after dispensing. The Hawai'i Narcotics Enforcement Division (NED) partnered with the University of Hawai'i at Hilo Daniel K. Inouye College of Pharmacy (CoP) in eleven Drug Take Back events throughout the state. Most participants heard of the events via newspaper and television marketing. The most common methods of medication disposal are via trash or down household drains. Over 8,000 lbs of unused/unwanted medications was collected, identified and logged from 2011 through 2012. The majority of returned drugs were non-controlled substances (90%). Commonly returned medications included prescription cardiac medications such as simvastatin and lisinopril, non-prescription analgesics such as aspirin and ibuprofen, and dietary supplements such as vitamins and iron. Commonly returned controlled substance medications included narcotics such as hydrocodone/acetaminophen combinations and oxycodone, and sedative hypnotics such as zolpidem and lorazepam.

  9. Crystallography and Drug Design

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 12. Crystallography and Drug Design. K Suguna. General Article Volume 19 Issue 12 December 2014 pp 1093-1103. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/019/12/1093-1103. Keywords.

  10. Computer aided drug design

    Science.gov (United States)

    Jain, A.

    2017-08-01

    Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.

  11. Perception and knowledge about narcotics among nurses

    Directory of Open Access Journals (Sweden)

    Desai Geetha

    2003-01-01

    Full Text Available Aim: To determine the extent to which nurses are able to correctly identify drugs as narcotics and to ascertain their perception of the addiction potential of opiates when used for pain management. Methods: A questionnaire was administered to 86 nurses who attended palliative care workshops in India. Findings: Only morphine (95%, heroin (71% and codeine (75% were correctly identified as narcotics by the majority of participants. Imipramine (34%, diazepam (20% and phenobarbitone (39% were wrongly classified as narcotics by many nurses. Dextropropoxyphene (11%, pentazocine (21%, buprenorphine (15% were correctly classified as narcotics by fewer than half the participants. Only 14% knew that that the frequency of psychological dependence due to use of morphine for cancer pain was less than 1%.

  12. Detection of narcotics with an immunoassay film badge

    International Nuclear Information System (INIS)

    Lukens, H.R.

    1993-01-01

    Efficient personnel performance, a major requirement for a safe nuclear industry, is jeopardized where personnel use narcotics. However, detection of narcotics at nuclear plants is a challenge. The unique specificity and sensitivity of an immunoassay has been implemented in the form of a small, dry immunoassay film badge (IFB) for the detection of vapors emitted by narcotics. The device is suitable as an area monitor, and its characteristics are suitable for use as a breath monitor for the detection of drug use

  13. 75 FR 42487 - Supplementary Identifying Information of Previously-Designated Individual, Foreign Narcotics...

    Science.gov (United States)

    2010-07-21

    ... State, and the Secretary of Homeland Security when designating and blocking the property and interests... in, or providing financial or technological support for or to, or providing goods or services in... Agustin, Colombia; DOB 19 Feb 1976; Citizen Colombia; Cedula No. 79928745 (Colombia); Passport AF392658...

  14. Development of a portable preconcentrator/ion mobility spectrometer system for the trace detection of narcotics

    Energy Technology Data Exchange (ETDEWEB)

    Parmeter, J.E.; Custer, C.A.

    1997-08-01

    This project was supported by LDRD funding for the development and preliminary testing of a portable narcotics detection system. The system developed combines a commercial trace detector known as an ion mobility spectrometer (IMS) with a preconcentrator originally designed by Department 5848 for the collection of explosives molecules. The detector and preconcentrator were combined along with all necessary accessories onto a push cart, thus yielding a fully portable detection unit. Preliminary testing with both explosives and narcotics molecules shown that the system is operational, and that it can successfully detect drugs as marijuana, methamphetamine (speed), and cocaine based on their characteristics IMS signatures.

  15. Drug Design and Emotion

    Science.gov (United States)

    Folkers, Gerd; Wittwer, Amrei

    2007-11-01

    "Geteiltes Leid ist halbes Leid." The old German proverb reflects the fact that sharing a bad emotion or feeling with someone else may lower the psychological strain of the person experiencing sorrow, mourning or anger. On the other hand the person showing empathy will take literally a load from its counterpart, up to physiological reaction of the peripheral and central nervous pain system. Though subjective, mental and physical states can be shared. Visual perception of suffering may be important but also narrative description plays a role, all our senses are mixing in. It is hypothetized that literature, art and humanities allow this overlap. A change of mental states can lead to empirically observable effects as it is the case for the effect of role identity or placebo on pain perception. Antidepressants and other therapeutics are another choice to change the mental and bodily states. Their development follows today's notion of "rationality" in the design of therapeutics and is characterized solely by an atomic resolution approach to understand drug activity. Since emotional states and physiological states are entangled, given the difficulty of a physical description of emotion, the future rational drug design should encompass mental states as well.

  16. Pain medications - narcotics

    Science.gov (United States)

    ... other medical problems does not itself lead to dependence. Store narcotics safely and securely in your home. ... help with constipation, drink more fluids, get more exercise, eat foods with extra fiber, and use stool ...

  17. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  18. Effectiveness of Hope Therapy on Reducing Depressive Symptoms and Preventing of Relapse in Cure-Seeker Women with Dependency to Narcotic Drugs

    Directory of Open Access Journals (Sweden)

    Akram S Raesian

    2011-05-01

    Full Text Available Introduction: The aim of the present research was the investigation of the effectiveness of hope therapy on reduction of the degree of depression symptoms and prevention of relapse in cure-seeker women with dependency to narcotic drugs. Method: In semi-experimental research method 20 clients who diagnosed as substance abuse disorder that completed detoxification period successfully, and they were scored more than 14 in depression symptoms (Beck depression questionnaire, second edition selected by available sampling and assigned to two experimental (n=10 and witness (n=10 groups randomly. Experimental group was trained for 8 sessions under training of hope therapy and witness group was not under any training. The experimental peple were evaluated by Snyder Hope scale and Beck depression questionnaire and morphine test before beginning of therapy. After it and after the completition of the two months follow-up period. For analyzing of data chi square test, Z test, and ANCOVA were applied. Results: The results showed that hope therapy education could create considerable reduction in degree of depression symptoms of women suffering from addiction. In addition, results of chi square test indicated significant difference between the number of relapsed women in experimental and witness groups. Conclusion: in general, results of this survey show that hope therapy education is effective in reduction of degree of depression symptoms and prediction of relapse in cure-seeker women suffering from addiction.

  19. 7 CFR 500.7 - Intoxicating beverages and narcotics.

    Science.gov (United States)

    2010-01-01

    ..., by a person under the influence of intoxicating beverages or a narcotic drug, is prohibited. (b... USNA property is prohibited. (c) The sale of alcoholic beverages on the grounds of the USNA is...

  20. Personality Disorders, Narcotics, and Stimulants; Relationship in Iranian Male Substance Dependents Population.

    Science.gov (United States)

    Noorbakhsh, Simasadat; Zeinodini, Zahra; Khanjani, Zeynab; Poorsharifi, Hamid; Rajezi Esfahani, Sepideh

    2015-06-01

    Individuals with certain personality disorders, especially the antisocial and borderline personality disorders, are more prone to substance use disorders. Regarding the importance of substance use disorders, this study aimed to explore the association between personality disorders and types of used drugs (narcotics and stimulants) in Iranian male substance users. The current study was a correlation study. We evaluated 285 male substance users and excluded 25 according to exclusion criteria. A total of 130 narcotic users and 130 stimulant users were recruited randomly in several phases from January 2013 to October 2013. All participants were referred to Substance Dependency Treatment Clinics in Tehran, Iran. Data collection process was accomplished by means of clinical interview based on DSM-V criteria for substance use disorders, Iranian version of addiction severity index (ASI), and Millon clinical multi-axial inventory-III (MCMI-III). Data were analyzed by SPSS 21 using Pearson correlation coefficient and regression, the. There was a significant correlation between stimulant use and histrionic personality disorder (P personality disorders (P histrionic, and narcissistic personality disorders (P personality disorders (P personality disorders, and narcotic and stimulants consumption (P personality disorder and narcotics (P personality disorders and types of used drugs were in accordance with the previous studies results. It is necessary to design appropriate treatment plans for medical treatment of those with personality disorders.

  1. Antecedents of narcotic use and addiction. A study of 898 Vietnam veterans.

    Science.gov (United States)

    Helzer, J E; Robins, L N; Davis, D H

    1976-02-01

    Previous studies of predictors of narcotic abuse have been retrospective and based on samples of long-term addicts obtained from legal or medical channels. There are several methodological problems in this approach. The present study is an attempt to test certain alleged predictors of narcotic use in a cohort of 898 Vietnam veterans. The design overcomes several of the methodological weaknesses of previous studies. Eight variables which have been reported as predictors of drug use or addiction in the drug literature were inquired about during a personal interview which included the premilitary life of each subject. The antecedent variables were socioeconomic background, inner city residence, psychiatric illness, broken home, race, employment history, education and antisocial history. Using information obtained from interviews and military records, we then tested the predictive value of each of these antecedents by comparing narcotic used and addiction in Vietman and use after Vietnam in men differing with respect to each antecedent. Results indicate that some of the variables were very poor, and others very good predictors of the various levels of narcotic involvement. The predictive value and overall importance of each of the variables we tested are discussed.

  2. Crystallography and Drug Design

    Indian Academy of Sciences (India)

    IAS Admin

    is of immense help in developing drugs for specific diseases by targeting molecules ... tions, or selected from a large pool of available libraries and the binding strengths can ... was identified to be caused by a virus named later as the human.

  3. Rational drug design paradigms: the odyssey for designing better drugs.

    Science.gov (United States)

    Kellici, Tahsin; Ntountaniotis, Dimitrios; Vrontaki, Eleni; Liapakis, George; Moutevelis-Minakakis, Panagiota; Kokotos, George; Hadjikakou, Sotiris; Tzakos, Andreas G; Afantitis, Antreas; Melagraki, Georgia; Bryant, Sharon; Langer, Thierry; Di Marzo, Vincenzo; Mavromoustakos, Thomas

    2015-01-01

    Due to the time and effort requirements for the development of a new drug, and the high attrition rates associated with this developmental process, there is an intense effort by academic and industrial researchers to find novel ways for more effective drug development schemes. The first step in the discovery process of a new drug is the identification of the lead compound. The modern research tendency is to avoid the synthesis of new molecules based on chemical intuition, which is time and cost consuming, and instead to apply in silico rational drug design. This approach reduces the consumables and human personnel involved in the initial steps of the drug design. In this review real examples from our research activity aiming to discover new leads will be given for various dire warnings diseases. There is no recipe to follow for discovering new leads. The strategy to be followed depends on the knowledge of the studied system and the experience of the researchers. The described examples constitute successful and unsuccessful efforts and reflect the reality which medicinal chemists have to face in drug design and development. The drug stability is also discussed in both organic molecules and metallotherapeutics. This is an important issue in drug discovery as drug metabolism in the body can lead to various toxic and undesired molecules.

  4. Drug Take Back in Hawai‘i: Partnership Between the University of Hawai‘i Hilo College of Pharmacy and the Narcotics Enforcement Division

    OpenAIRE

    Ma, Carolyn S; Batz, Forrest; Juarez, Deborah Taira; Ladao, Lani C

    2014-01-01

    Unused/unwanted medications in households and patient care facilities expose vulnerable populations, including children, elders, and pets, to potential harm through inadvertent ingestion, as well as the potential for theft and assault. Hawai‘i Administrative Rules prohibit the return of any prescription medications to retail pharmacies after dispensing. The Hawai‘i Narcotics Enforcement Division (NED) partnered with the University of Hawai‘i at Hilo Daniel K. Inouye College of Pharmacy (CoP) ...

  5. Pyrimidines in antimalarial drug design

    CSIR Research Space (South Africa)

    Moleele, SS

    2008-09-01

    Full Text Available of the routes attempted are shown in Scheme 1. Pyrimidines In Antimalarial Drug Design S S Moleele1, D Gravestock1, A L Rousseau1, R L Van Zyl2 1Discovery Chemistry, CSIR, Biosciences, Private Bag X2, Modderfontein, 1645, South Africa; SMoleele@csir.co.za 2...

  6. New Challenges in the Narcotics World

    Directory of Open Access Journals (Sweden)

    Nicoleta-Elena Buzatu

    2011-05-01

    Full Text Available The consumption of narcotics is one of the problems the international world is confronted withnowadays; its direct or indirect effects lead to the conclusion that it represents a worrying phenomenon meantto be taken into account by the international programs of co-operation. In contrast with the mature population,the younger population is much more receptive to the new, much more attracted by new experiments and,consequently, by risks. The narcotics flagellum is one of the most complex, profound and dramaticphenomena met with in the contemporary world. Narcotization is the morbid habit of repeatedly taking andusing ever higher doses of more or less toxic substances able to generate a psychological and physicaladdiction to them. Unhappily due to the lack of information, people think that the illegal substances only –heroine, marijuana, cocaine, etc. – are considered drugs. Not long ago there appeared the so-called “mixes ofethno-botanical plants” that are perfectly legal, and many consumers have replaced narcotics - as marijuana,for example - with plant mixes. According to explanations given by the Ethno-botanical ExplanatoryDictionary, ethno-biology is a branch that studies the mutual relationship between man and plant. InRomania, ethno-botanical plants are sold under the generic names of “aroma therapeutic” or “ethnobotanical”plants. The numerous researches meant to decode the molecular and biochemical structure of theseherbs, the researchers found that consumers are described as facing hallucinogenic effects caused by somesynthetic substances - cannabinoids - added by manufacturers.

  7. Fragment-based drug design.

    Science.gov (United States)

    Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

    2011-01-01

    Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.

  8. THE EFFECT OF ILLICIT TRADE IN NARCOTICS ON GLOBAL ECONOMY

    Directory of Open Access Journals (Sweden)

    ALASMARI Khaled

    2013-07-01

    Illicit markets especially those dealing with narcotics constitute grievous issues to the world’s economies, putting to test global safety, economic progress as well as security and many other aspects. Seemingly, illicit narcotics trade in the last decade – that is 2000 to 2011 underwent a significant boom, resulting from a wide spectrum of illegal drugs such as cocaine as well as heroin among many other hard drugs. In today’s global society, several concerns are emerging on the rise of illicit narcotics trade accompanied with organized crime, chiefly as major hindrances to consistent global economic progress. Apparently, some of the effects of illicit narcotics trade are that; this trade gradually turns upside down business rules, opening way for new unruly market players besides reconfiguring influence in global economics as well as politics. Surprisingly, the revenue from illegal drugs in 2011 alone was roughly 10% of the global GDP. Hence, exaggerating local economies’ incomes and triggering ceaseless conflicts among market players, while at the same time reducing legal business activities likewise disintegrating socioeconomic conditions. An empirical research method was adopted for this study, analyzing illicit trade in narcotics on the global arena as from 2000 to 2011 and its resultant effects. The research findings indicate that, illegal drugs trade particularly on the world economy besides growing at a high rate, it endangers the overall welfare of humans likewise the business environment. This is ostensibly because this trade has high chances of engrossing regional economies into illegal drugs business activities, causing them to neglect sustainable ethical businesses. Now, to effectively address negative economic issues related to illegal drugs trade, there is apparent need for integrated efforts from local as well as international authorities. Such efforts are chiefly to control not only the harmful effects resulting from the use of illicit

  9. Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study.

    Science.gov (United States)

    de Abajo, Francisco J; Gil, Miguel J; García Poza, Patricia; Bryant, Verónica; Oliva, Belén; Timoner, Julia; García-Rodríguez, Luis A

    2014-11-01

    The purpose of this study is to estimate the risk of nonfatal acute myocardial infarction (AMI) associated with traditional NSAIDs (tNSAIDs), non-narcotic analgesics (paracetamol and metamizole), and symptomatic slow-acting drugs in osteoarthritis (SYSADOAs) overall and in different subgroups of patients. We performed a nested case-control study using a Primary Care Database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria), over the study period, 2001-2007. We included patients aged 40-90 years, with nonfatal AMI and randomly selected controls matched for age, sex and calendar year. Exposure to drugs was assessed within a 30-day window before the index date. We did not find an association with nonfatal AMI in patients at low-intermediate background cardiovascular risk (odds ratio = 0.92; 95% confidence interval: 0.76-1.12), whereas there was a moderate significant association among those at high risk (1.28; 1.06-1.54) or when tNSAIDs were used for longer than 365 days (1.43; 1.12-1.82). The greatest risk occurred when these two conditions were combined (1.80; 1.26-2.58). The risk varied across individual tNSAIDs, with ibuprofen (0.95; 0.78-1.16) in the lower and aceclofenac (1.59; 1.15-2.19) in the upper part of the range. Low-dose aspirin did not modify the risk profile showed by any of the individual tNSAIDs examined. Paracetamol (0.84; 0.74-0.95), metamizole (1.06; 0.87-1.29) and SYSADOAs (0.68; 0.47-0.99) were not associated with an increased risk overall or in any subgroup of patients. The risk of nonfatal AMI varied with individual tNSAIDs, duration of treatment and background cardiovascular risk. Paracetamol, metamizole and SYSADOAs did not increase the risk in any of the conditions examined. Copyright © 2014 John Wiley & Sons, Ltd.

  10. The Efficacy of Foreign Assistance in Counter Narcotics

    Science.gov (United States)

    2013-03-01

    ACI Were Initiated. ...........................................................................................................15 Figure 3. Coffee ...Crop Reduction Components)...................................................................................25 Table 6. Colombian Coffee Prices in U.S...drug trafficking. Due to the covert nature of narcotics transactions, scholars are limited to estimations based on coca, poppy, and cannabis

  11. [Narcotic abuse in Jylland. A study based on narcotics and deaths of addicts examined at the Institute of Forensic Medicine, University of Aarhus during the period 1981-1988. 1. Narcotics].

    Science.gov (United States)

    Kaa, E

    1990-04-09

    On the basis of analysis of 1,879 samples of narcotics confiscated in Jutland and Funen during the period 1981-1988, the individual types of drugs are described as regards occurrence and quality. Cannabis and heroin were found in the illegal market during the entire period. Amphetamine was rarely observed prior to 1985 but comprised half of the illegal drugs examined in 1988. Cocaine was encountered in only 1% of the samples. Designer drugs were not seen. Heroin occurred relatively most frequently in Aarhus, Odense and Esbjerg while amphetamine and cannabis were found in all parts of Jutland and Funen. The samples of heroin and amphetamine varied greatly as regards strength and the types and quantities of cutting agents. The majority of the samples were adulterated and/or diluted with substances such as caffeine and phenazone and the sugars, glucose and lactose.

  12. Greater number of narcotic analgesic prescriptions for osteoarthritis is associated with falls and fractures in elderly adults.

    Science.gov (United States)

    Rolita, Lydia; Spegman, Adele; Tang, Xiaoqin; Cronstein, Bruce N

    2013-03-01

    To evaluate the changes in types of medications prescribed for pain before and after withdrawal of certain selective cyclooxygenase 2 (COX-2) inhibitors in 2004 and to determine whether there was an association with fall events in elderly adults with a diagnosis of osteoarthritis (OA). A nested case-control design using electronic medical records compiled between 2001 and 2009. Electronic medical records for care provided in an integrated health system in rural Pennsylvania over a 9-year period (2001-09), the midpoint of which rofecoxib and valdecoxib were pulled from the market. Thirteen thousand three hundred fifty-four individuals aged 65 to 89 with a diagnosis of OA. The incidence of falls and fractures was examined in relation to analgesics prescribed: narcotics, COX-2 inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs). The comparison sample of individuals who did not fall was matched 3:1 with those who fell according to age, sex, and comorbidity. Narcotic analgesic prescriptions were associated with a significantly greater risk of falls and fractures. The likelihood of experiencing a fall/fracture was higher in participants prescribed narcotic analgesics than those prescribed a COX-2 inhibitor (odds ratio (OR) = 3.3, 95% confidence interval (CI) = 2.5-4.3) or NSAID (OR = 4.1, 95% CI = 3.7-4.5). Use of narcotic analgesics is associated with risk of falls and fractures in elderly adults with OA, an observation that suggests that the current guidelines for the treatment of pain, which include first-line prescription of narcotics, should be reevaluated. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

  13. Early intravenous ibuprofen decreases narcotic requirement and length of stay after traumatic rib fracture.

    Science.gov (United States)

    Bayouth, Lilly; Safcsak, Karen; Cheatham, Michael L; Smith, Chadwick P; Birrer, Kara L; Promes, John T

    2013-11-01

    Pain control after traumatic rib fracture is essential to avoid respiratory complications and prolonged hospitalization. Narcotics are commonly used, but adjunctive medications such as nonsteroidal anti-inflammatory drugs may be beneficial. Twenty-one patients with traumatic rib fractures treated with both narcotics and intravenous ibuprofen (IVIb) (Treatment) were retrospectively compared with 21 age- and rib fracture-matched patients who received narcotics alone (Control). Pain medication requirements over the first 7 hospital days were evaluated. Mean daily IVIb dose was 2070 ± 880 mg. Daily intravenous morphine-equivalent requirement was 19 ± 16 vs 32 ± 24 mg (P pain scores were lower in the Treatment group (P rib fractures significantly decreases narcotic requirement and results in clinically significant decreases in hospital length of stay. IVIb therapy should be initiated in patients with traumatic rib fractures to improve patient comfort and reduce narcotic requirement.

  14. 32 CFR 228.9 - Prohibition on narcotics and illegal substances.

    Science.gov (United States)

    2010-07-01

    ... DEFENSE (CONTINUED) MISCELLANEOUS SECURITY PROTECTIVE FORCE § 228.9 Prohibition on narcotics and illegal... cases where the drug is being used as prescribed for a patient by a licensed physician. ...

  15. Computer Aided Drug Design: Success and Limitations.

    Science.gov (United States)

    Baig, Mohammad Hassan; Ahmad, Khurshid; Roy, Sudeep; Ashraf, Jalaluddin Mohammad; Adil, Mohd; Siddiqui, Mohammad Haris; Khan, Saif; Kamal, Mohammad Amjad; Provazník, Ivo; Choi, Inho

    2016-01-01

    Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.

  16. "9th Annual Congress on Drug Formulation & Drug Design"

    OpenAIRE

    Monty Karl

    2017-01-01

    Conference Series has been instrumental in conducting international meetings for seven years, and very excited to expand Europe, America and Asia Pacific continents. Previous meetings were held in major cities like Belgium, Tokyo, Madrid, with success the meetings again scheduled in three continents. It’s time to announce 9th Annual Congress on Drug Formulation & Drug Design October 19-21, 2017 Seoul, South Korea . Drug Formulation 2017 is a 3-day event offering the Exhibition, at venue to sh...

  17. Drug plan design incentives among Medicare prescription drug plans.

    Science.gov (United States)

    Huskamp, Haiden A; Keating, Nancy L; Dalton, Jesse B; Chernew, Michael E; Newhouse, Joseph P

    2014-07-01

    Medicare Advantage prescription drug plans (MA-PDs) and standalone prescription drug plans (PDPs) face different incentives for plan design resulting from the scope of covered benefits (only outpatient drugs for PDPs versus all drug and nondrug services for Medicare Advantage [MA]/MA-PDs). The objective is to begin to explore how MA-PDs and PDPs may be responding to their different incentives related to benefit design. We compared 2012 PDP and MA-PD average formulary coverage, prior authorization (PA) or step therapy use, and copayment requirements for drugs in 6 classes used commonly among Medicare beneficiaries. We primarily used 2012 Prescription Drug Plan Formulary and Pharmacy Network Files and MA enrollment data. 2011 Truven Health MarketScan claims were used to estimate drug prices and to compute drug market share. Average coverage and PA/step rates, and average copayment requirements, were weighted by plan enrollment and drug market share. MA-PDs are generally more likely to cover and less likely to require PA/step for brand name drugs with generic alternatives than PDPs, and MA-PDs often have lower copayment requirements for these drugs. For brands without generics, we generally found no differences in average rates of coverage or PA/step, but MA-PDs were more likely to cover all brands without generics in a class. We found modest, confirmatory evidence suggesting that PDPs and MA-PDs respond to different incentives for plan design. Future research is needed to understand the factors that influence Medicare drug plan design decisions.

  18. Thermodynamic Studies for Drug Design and Screening

    Science.gov (United States)

    Garbett, Nichola C.; Chaires, Jonathan B.

    2012-01-01

    Introduction A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically-driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development towards an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. PMID:22458502

  19. Thermodynamic studies for drug design and screening.

    Science.gov (United States)

    Garbett, Nichola C; Chaires, Jonathan B

    2012-04-01

    A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 - 2011 using the Science Citation Index and PUBMED and the keywords listed below. The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development toward an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in the design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. © 2012 Informa UK, Ltd.

  20. Metabolism of designer drugs of abuse.

    Science.gov (United States)

    Staack, Roland F; Maurer, Hans H

    2005-06-01

    Abuse of designer drugs is widespread among young people, especially in the so-called "dance club scene" or "rave scene", worldwide. Severe and even fatal poisonings have been attributed to the consumption of such drugs of abuse. However, in contrast to new medicaments, which are extensively studied in controlled clinical studies concerning metabolism, including cytochrome P450 isoenzyme differentiation, and further pharmacokinetics, designer drugs are consumed without any safety testing. This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4-methylthioamphetamine (4-MTA), were taken into consideration as new "classical" amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3, 4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) were taken into consideration as derivatives of the class of piperazine-derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha-pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing identification of in vivo or in vitro human or animal metabolites and cytochrome P450 isoenzyme dependent metabolism have been considered and summarized.

  1. Computer-Aided Drug Design in Epigenetics

    Directory of Open Access Journals (Sweden)

    Wenchao Lu

    2018-03-01

    Full Text Available Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

  2. Computer-Aided Drug Design in Epigenetics

    Science.gov (United States)

    Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

    2018-01-01

    Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation, and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field. PMID:29594101

  3. Computer-Aided Drug Design in Epigenetics

    Science.gov (United States)

    Lu, Wenchao; Zhang, Rukang; Jiang, Hao; Zhang, Huimin; Luo, Cheng

    2018-03-01

    Epigenetic dysfunction has been widely implicated in several diseases especially cancers thus highlights the therapeutic potential for chemical interventions in this field. With rapid development of computational methodologies and high-performance computational resources, computer-aided drug design has emerged as a promising strategy to speed up epigenetic drug discovery. Herein, we make a brief overview of major computational methods reported in the literature including druggability prediction, virtual screening, homology modeling, scaffold hopping, pharmacophore modeling, molecular dynamics simulations, quantum chemistry calculation and 3D quantitative structure activity relationship that have been successfully applied in the design and discovery of epi-drugs and epi-probes. Finally, we discuss about major limitations of current virtual drug design strategies in epigenetics drug discovery and future directions in this field.

  4. Designer Drug Confusion: A Focus on MDMA.

    Science.gov (United States)

    Beck, Jerome; Morgan, Patricia A.

    1986-01-01

    Discusses the competing definitions and issues surrounding various designer drugs, primarily 3, 4-methylenedioxy-methamphetamine (MDMA). Offers a rationale for why interest in MDMA, which possesses both stimulant and psychedelic properties, will continue to grow despite the drug's recent illegality and increasing evidence of neurotoxicity.…

  5. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    International Nuclear Information System (INIS)

    Smith, Clyde

    2005-01-01

    According to Smith, protein crystallography allows scientists to design drugs in a much more efficient way than the standard methods traditionally used by large drug companies, which can cost close to a billion dollars and take 10 to 15 years. 'A lot of the work can be compressed down,' Smith said. Protein crystallography enables researchers to learn the structure of molecules involved in disease and health. Seeing the loops, folds and placement of atoms in anything from a virus to a healthy cell membrane gives important information about how these things work - and how to encourage, sidestep or stop their functions. Drug design can be much faster when the relationship between structure and function tells you what area of a molecule to target. Smith will use a timeline to illustrate the traditional methods of drug development and the new ways it can be done now. 'It is very exciting work. There have been some failures, but many successes too.' A new drug to combat the flu was developed in a year or so. Smith will tell us how. He will also highlight drugs developed to combat HIV, Tuberculosis, hypertension and Anthrax.

  6. LEGO-inspired drug design

    DEFF Research Database (Denmark)

    Thanh Tung, Truong; Dao, Trong Tuan; Grifell Junyent, Marta

    2018-01-01

    The fungal plasma membrane H+-ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure-activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for design...

  7. AN ADDRESS DELIVERED BEFORE SCOPE'S CONFERENCE FOR EDUCATORS ON NARCOTICS AND SMOKING. (TITLE SUPPLIED).

    Science.gov (United States)

    RICE, JULIUS T.

    A SHORT HISTORY OF NARCOTICS USAGE IS PRESENTED. THE TERM DRUG DEPENDENCE IS BEING SUBSTITUTED FOR DRUG ADDICTION AND DRUG HABITUATION. THE ADVANTAGES AND DISADVANTAGES OF VARIOUS ANTIDOTES FOR OPIATES ARE DESCRIBED. THE EFFECTS OF LSD AND MARIJUANA ON PHYSICAL AND MENTAL PROCESSES ARE DESCRIBED. THE USE OF LSD FOR MEDICAL PURPOSES IS DISCUSSED.…

  8. IMPLEMENTATION OF DRUG ADDICTS RIGHT TO HEALTH PROTECTION (SEPARATE ASPECTS).

    Science.gov (United States)

    Shevchuk, O; Rzhevska, O; Korop, O; Pyliuha, L

    2018-03-01

    The purpose of the research is to analyze specific problems of the realization of the right to protect the health of people who take narcotic drugs or psychotropic substances. To achieve this goal, statistics have been analyzed on the number of people using narcotic drugs or psychotropic substances (including drug-addicted children) placed on medical records and the number of their applications for medical care. It has been found out that people in this category often face a denial of medical care that causes extremely strong physical and mental suffering. The analysis of the understanding of the legal design of the «right to health care» in the scientific literature, national legislation and international legal documents was made. State institutions and local authorities providing «the right to health care» of people taking narcotic or psychotropic drugs are singled out. The absence of grounds for restricting the right to protect the health of people who take narcotic or psychotropic drugs who are not registered is justified. In the course of the research, it was found out that people who take narcotic drugs or psychotropic substances are more likely than other patients to need medical assistance and, when requesting the right to health care, face a number of problems that require immediate solution: incomplete provision of quality free medical care; unimplementation of rehabilitation programs for such categories of patients; the lack of the right of children who take narcotic drugs or psychotropic substances to make their own decisions at the age of 14 and apply to public health institutions for the treatment of drug addiction; violations of the continuity of SMT programs and their absence in penal institutions for drug dependent people. It was proposed to introduce a number of changes in the relevant normative legal acts.

  9. Targeted proteins for diabetes drug design

    Science.gov (United States)

    Doan Trang Nguyen, Ngoc; Thi Le, Ly

    2012-03-01

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people.

  10. Targeted proteins for diabetes drug design

    International Nuclear Information System (INIS)

    Trang Nguyen, Ngoc Doan; Le, Ly Thi

    2012-01-01

    Type 2 diabetes mellitus is a common metabolism disorder characterized by high glucose in the bloodstream, especially in the case of insulin resistance and relative insulin deficiency. Nowadays, it is very common in middle-aged people and involves such dangerous symptoms as increasing risk of stroke, obesity and heart failure. In Vietnam, besides the common treatment of insulin injection, some herbal medication is used but no unified optimum remedy for the disease yet exists and there is no production of antidiabetic drugs in the domestic market yet. In the development of nanomedicine at the present time, drug design is considered as an innovative tool for researchers to study the mechanisms of diseases at the molecular level. The aim of this article is to review some common protein targets involved in type 2 diabetes, offering a new idea for designing new drug candidates to produce antidiabetic drugs against type 2 diabetes for Vietnamese people. (review)

  11. 21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

    Science.gov (United States)

    2010-04-01

    ...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan...

  12. Drug Abuse in the New York City Schools. A Report of the Select Committee on Narcotics Abuse and Control, House of Representatives, Ninety-Fifth Congress, Second Session (August 30-September 1, 1978).

    Science.gov (United States)

    Congress of the U.S., Washington, DC.

    The January 1977 hearing by the U.S. House Select Committee on Narcotics Abuse and Control mandated three days of further hearings in 1978. The focus was upon New York city schools, but reflected many similar situations in other urban school systems according to the committee's judgement. The committee also found that alcohol and marihuana usage…

  13. Defining Patient Centric Pharmaceutical Drug Product Design.

    Science.gov (United States)

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

  14. In silico fragment-based drug design.

    Science.gov (United States)

    Konteatis, Zenon D

    2010-11-01

    In silico fragment-based drug design (FBDD) is a relatively new approach inspired by the success of the biophysical fragment-based drug discovery field. Here, we review the progress made by this approach in the last decade and showcase how it complements and expands the capabilities of biophysical FBDD and structure-based drug design to generate diverse, efficient drug candidates. Advancements in several areas of research that have enabled the development of in silico FBDD and some applications in drug discovery projects are reviewed. The reader is introduced to various computational methods that are used for in silico FBDD, the fragment library composition for this technique, special applications used to identify binding sites on the surface of proteins and how to assess the druggability of these sites. In addition, the reader will gain insight into the proper application of this approach from examples of successful programs. In silico FBDD captures a much larger chemical space than high-throughput screening and biophysical FBDD increasing the probability of developing more diverse, patentable and efficient molecules that can become oral drugs. The application of in silico FBDD holds great promise for historically challenging targets such as protein-protein interactions. Future advances in force fields, scoring functions and automated methods for determining synthetic accessibility will all aid in delivering more successes with in silico FBDD.

  15. Designer drugs: how dangerous are they?

    NARCIS (Netherlands)

    Reneman, L.

    2003-01-01

    Of the designer drugs, the amphetamine analogues are the most popular and extensively studied, ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in particular. They are used recreationally with increasing popularity despite animal studies showing neurotoxic effects to serotonin (5-HT) and/or

  16. Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

    Directory of Open Access Journals (Sweden)

    Apurv Patel

    2016-01-01

    Full Text Available The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients.

  17. Modeling chemical reactions for drug design.

    Science.gov (United States)

    Gasteiger, Johann

    2007-01-01

    Chemical reactions are involved at many stages of the drug design process. This starts with the analysis of biochemical pathways that are controlled by enzymes that might be downregulated in certain diseases. In the lead discovery and lead optimization process compounds have to be synthesized in order to test them for their biological activity. And finally, the metabolism of a drug has to be established. A better understanding of chemical reactions could strongly help in making the drug design process more efficient. We have developed methods for quantifying the concepts an organic chemist is using in rationalizing reaction mechanisms. These methods allow a comprehensive modeling of chemical reactivity and thus are applicable to a wide variety of chemical reactions, from gas phase reactions to biochemical pathways. They are empirical in nature and therefore allow the rapid processing of large sets of structures and reactions. We will show here how methods have been developed for the prediction of acidity values and of the regioselectivity in organic reactions, for designing the synthesis of organic molecules and of combinatorial libraries, and for furthering our understanding of enzyme-catalyzed reactions and of the metabolism of drugs.

  18. The politics of narcotic drugs: a survey

    National Research Council Canada - National Science Library

    Buxton, Julia

    2011-01-01

    ... or transmitted in any form or by any electronic or mechanical means without the prior permission of the copyright owner. ISBN 0-203-83886-6 Master e-book ISBN ISBN 978-1-85743-501-6 (hbk) ISBN 978-0-203-83886-0 (ebk) Editor Europa New Projects: Cathy Hartley The publishers make no representation, express or implied, with regard to ...

  19. Drug design: Insights from atomistic simulations

    International Nuclear Information System (INIS)

    Collu, F.; Spiga, E.; Kumar, A.; Hajjar, E.; Vargiu, A.V.; Ceccarelli, M.; Ruggerone, P.

    2009-01-01

    Computer simulations have become a widely used and powerful tool to study the behaviour of many-particle and many-interaction systems and processes such as nucleic acid dynamics, drug-DNA interactions, enzymatic processes, membrane, antibiotics. The increased reliability of computational techniques has made possible to plane a bottom-up approach in drug design, i.e. designing molecules with improved properties starting from the knowledge of the molecular mechanisms. However, the in silico techniques have to face the fact that the number of degrees of freedom involved in biological systems is very large while the time scale of several biological processes is not accessible to standard simulations. Algorithms and methods have been developed and are still under construction to bridge these gaps. Here we review the activities of our group focussed on the time-scale bottleneck and, in particular, on the use of the meta dynamics scheme that allows the investigation of rare events in reasonable computer time without reducing the accuracy of the calculation. In particular, we have devoted particular attention to the characterization at microscopic level of translocation of antibiotics through membrane pores, aiming at the identification of structural and dynamical features helpful for a rational drug design.

  20. Afghanistan Narcotics: The Bigger Battle Toward Stabilization

    Science.gov (United States)

    2009-04-01

    composition of the region limit agricultural output and the availability of successful crops. Energy resources, precious metals, and gemstones are...narcotics industry. Afghanistan should consider oil, natural gas, coal, minerals, and gemstones as viable industrial options. Marketing of these

  1. Operational Design and Convergent Threats: A Comparison Case Study of Plan Colombia and Afghanistan Aimed to Enhance the Fight Against Narcotic-Funded Insurgencies

    Science.gov (United States)

    2012-05-17

    capacity to shape the environmental conditions and prevent root causes that foster malicious partnerships. This monograph advocates for increased... legislation through the Congress for various United Stated agencies, including the Departments of State, Justice, and Defense Legislation , expanded agency...behind the Colombian and Afghan drug trades are complex nodes of national and international organizations and individuals. 19 Both, Colombia and

  2. A structural keystone for drug design

    Directory of Open Access Journals (Sweden)

    Rother Kristian

    2006-06-01

    Full Text Available 3D-structures of proteins and potential ligands are the cornerstones of rational drug design. The first brick to build upon is selecting a protein target and finding out whether biologically active compounds are known. Both tasks require more information than the structures themselves provide. For this purpose we have built a web resource bridging protein and ligand databases. It consists of three parts: i A data warehouse on annotation of protein structures that integrates many well-known databases such as Swiss-Prot, SCOP, ENZYME and others. ii A conformational library of structures of approved drugs. iii A conformational library of ligands from the PDB, linking the realms of proteins and small molecules.

  3. JUVENILE CRIMES CONNECTED WITH NARCOTICS AND PSYCHOTROPIC SUBSTANCES TRAFFICKING: CRIMINOLOGICAL ASPECTS

    Directory of Open Access Journals (Sweden)

    Ms. Irina V. Tseveleva

    2016-06-01

    Full Text Available The article deals with criminological aspects of juvenile crime in the narcotics and psychotropic substances trafficking. The authors analyzed the main reasons of committing these crimes by teenagers. The proposals for the prevention of minors’ criminal behavior in drug trafficking are drafted.

  4. Phytosterols and anabolic agents versus designer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Brabander, H.F. de [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)]. E-mail: Hubert.DeBrabander@UGent.be; Verheyden, K. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Mortier, V. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium); Le Bizec, B. [LABERCA, Ecole Nationale Veterinaire de Nantes, BP 50707, F-44087 Nantes Cedex 03 (France); Verbeke, W. [Ghent University, Department of Agricultural Economics, Coupure links 653, B-9000 Ghent (Belgium); Courtheyn, D. [Federal Feed and Food Laboratory, Braemkasteelstraat 59, B-9050 Ghentbruges (Belgium); Noppe, H. [Ghent University, Faculty of Veterinary Medicine, Research group of Veterinary Public Health and Zoonoses, Laboratory of Chemical Analysis, Salisburylaan 133, B-9820 Merelbeke (Belgium)

    2007-03-14

    Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the {sup 13}C/{sup 12}C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse.

  5. Phytosterols and anabolic agents versus designer drugs

    International Nuclear Information System (INIS)

    Brabander, H.F. de; Verheyden, K.; Mortier, V.; Le Bizec, B.; Verbeke, W.; Courtheyn, D.; Noppe, H.

    2007-01-01

    Cholesterol is a well-known component in fats of animal origin and it also is the precursor of natural hormones. Phytosterols appear in plants and only differ slightly in structure from cholesterol. An important difference however is the low absorption in the gut of phytosterols and their saturated derivatives, the phytostanols. As a result, there is time for all kind of reactions in faecal material inside and outside of the gut. Determination of the abuse of natural hormones may be based on gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Abuse of natural hormones changes the 13 C/ 12 C ratio of some metabolites during a relatively long time. The formation of (natural) hormones in the gut may interfere with this method. Designer drugs are mainly known from sports doping. In animal fattening, designer drugs may be used as well. Small changes in the structure of (natural) hormones may lead to a new group of substances asking for new strategies for their detection and the constatation of their abuse

  6. e-Drug3D: 3D structure collections dedicated to drug repurposing and fragment-based drug design.

    Science.gov (United States)

    Pihan, Emilie; Colliandre, Lionel; Guichou, Jean-François; Douguet, Dominique

    2012-06-01

    In the drug discovery field, new uses for old drugs, selective optimization of side activities and fragment-based drug design (FBDD) have proved to be successful alternatives to high-throughput screening. e-Drug3D is a database of 3D chemical structures of drugs that provides several collections of ready-to-screen SD files of drugs and commercial drug fragments. They are natural inputs in studies dedicated to drug repurposing and FBDD. e-Drug3D collections are freely available at http://chemoinfo.ipmc.cnrs.fr/e-drug3d.html either for download or for direct in silico web-based screenings.

  7. Peculiarities of mental and behavioral disorders due to use of designer drugs among young population and problems of early diagnostics (literature review

    Directory of Open Access Journals (Sweden)

    Spirina I.D.

    2017-06-01

    Full Text Available The analysis of the data of the domestic and foreign literature regarding the dynamics of narcotization among children and adolescents is carried out. It has been established that at present the growth rates of the use of psychoactive substances by minors far outstrip those of the adult population. It is also determined that in most cases "adult" drug addiction is formed in a teenage environment and therefore adolescents are a group of high-risk narcotization. Besides, new types of additions are constantly added: non-opioid analgetics, antidepressants, pharmacy products based on medicinal plants with stimulating or sedative properties, new means of perfumery and household chemicals, volatile organic compounds, etc. In this regard, in the clinical picture of drug intoxication, new variations of affective, psycho-organic and psychosomatic effects and complications are noted. In recent years, synthetic cannabinoids has rapidly gained "popularity" among young people that are successfully promoted by marketers. They are the part of the so-called designer drugs, appearing in the markets in the form of bath salts, flavors, fertilizers for indoor plants and "smoking mixtures" - spices. The publications of domestic and foreign authors give a lot of evidence of the ability of these substances not only to cause a state of intoxication, alienation, relaxation, but also leads to dependence on them with severe consequences for the psyche and all organism as a whole. Thus, the powerful anthropogenic damaging effect of designer drugs demonstrates concrete signals of a threat to health, demography and the economy of the society as a result of their use by the population.

  8. Birth order and hospitalization for alcohol and narcotics use in Sweden.

    Science.gov (United States)

    Barclay, Kieron; Myrskylä, Mikko; Tynelius, Per; Berglind, Daniel; Rasmussen, Finn

    2016-10-01

    Previous studies have shown that birth order is an important predictor of later life health as well as socioeconomic attainment. In this study, we examine the relationship between birth order and hospitalization for alcohol and narcotics use in Sweden. We study the relationship between birth order and hospitalization related to alcohol and narcotics use before and after the age of 20 using Swedish register data for cohorts born 1987-1994. We apply Cox proportional hazard models and use sibling fixed effects, eliminating confounding by factors shared by the siblings. Before age 20 we find that later born siblings are hospitalized for alcohol use at a higher rate than first-borns, and there is a monotonic increase in the hazard of hospitalization with increasing birth order. Second-borns are hospitalized at a rate 47% higher than first-borns, and third-borns at a rate 65% higher. Similar patterns are observed for hospitalization for narcotics use. After age 20 the pattern is similar, but the association is weaker. These patterns are consistent across various sibling group sizes. Later born siblings are more likely to be hospitalized for both alcohol and narcotics use in Sweden. These birth order effects are substantial in size, and larger than the estimated sex differences for the risk of hospitalization related to alcohol and drug use before age 20, and previous estimates for socioeconomic status differences in alcohol and drug abuse. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Protein Crystallography: A 'Must' Technology for Drug Design

    International Nuclear Information System (INIS)

    Matsuzaki, Takao

    2004-01-01

    The history of drug-related protein crystallography and drug design is reviewed to show that 'Lead Generation' is high-lighted in the pharmaceutical industry nowadays. A new drug design method has been developed. The method gave very high success rate; 10-60 % gave < 100 μM, 90 % gave < 10 mM. The crystal structures of drug-protein complexes have become even more important to give solid experimental bases for e.g. 1,000 designed structures and to find the new mechanisms of drug action

  10. Prescription of the High Risk Narcotics and Trading or Illicit Purchasing of High Risk Narcotics

    Directory of Open Access Journals (Sweden)

    Nicoleta-Elena Buzatu

    2012-05-01

    Full Text Available The present essay will analyze the offence of prescribing high risk narcotics and trading or illicit purchasing of high risk narcotics, as it was regulated - together with other offences - by Law no 143 of July 26, 2000 on preventing and fighting against the traffic and illicit consumption of narcotics. The same law defines the meaning of such a phrase “substances which are under national control” by mentioning the fact that they are the narcotics and their precursors listed in Annexes I-IV of the law. The analysis of the offence of prescribing the high risk narcotics and trading or illicit purchasing of high risk narcotics is following the already known structure mentioned in the doctrine and which consists of: object and subjects of the offence, its constituent content: the objective side with its material element, the immediate consequence and causality connections; the subjective side of the offence, as well as forms and modalities of these offences, and the applicable sanctions, of course.

  11. Bioinformatics in cancer therapy and drug design

    International Nuclear Information System (INIS)

    Horbach, D.Y.; Usanov, S.A.

    2005-01-01

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)

  12. Bioinformatics in cancer therapy and drug design

    Energy Technology Data Exchange (ETDEWEB)

    Horbach, D Y [International A. Sakharov environmental univ., Minsk (Belarus); Usanov, S A [Inst. of bioorganic chemistry, National academy of sciences of Belarus, Minsk (Belarus)

    2005-05-15

    One of the mechanisms of external signal transduction (ionizing radiation, toxicants, stress) to the target cell is the existence of membrane and intracellular proteins with intrinsic tyrosine kinase activity. No wonder that etiology of malignant growth links to abnormalities in signal transduction through tyrosine kinases. The epidermal growth factor receptor (EGFR) tyrosine kinases play fundamental roles in development, proliferation and differentiation of tissues of epithelial, mesenchymal and neuronal origin. There are four types of EGFR: EGF receptor (ErbB1/HER1), ErbB2/Neu/HER2, ErbB3/HER3 and ErbB4/HER4. Abnormal expression of EGFR, appearance of receptor mutants with changed ability to protein-protein interactions or increased tyrosine kinase activity have been implicated in the malignancy of different types of human tumors. Bioinformatics is currently using in investigation on design and selection of drugs that can make alterations in structure or competitively bind with receptors and so display antagonistic characteristics. (authors)

  13. Molecular Rift: Virtual Reality for Drug Designers.

    Science.gov (United States)

    Norrby, Magnus; Grebner, Christoph; Eriksson, Joakim; Boström, Jonas

    2015-11-23

    Recent advances in interaction design have created new ways to use computers. One example is the ability to create enhanced 3D environments that simulate physical presence in the real world--a virtual reality. This is relevant to drug discovery since molecular models are frequently used to obtain deeper understandings of, say, ligand-protein complexes. We have developed a tool (Molecular Rift), which creates a virtual reality environment steered with hand movements. Oculus Rift, a head-mounted display, is used to create the virtual settings. The program is controlled by gesture-recognition, using the gaming sensor MS Kinect v2, eliminating the need for standard input devices. The Open Babel toolkit was integrated to provide access to powerful cheminformatics functions. Molecular Rift was developed with a focus on usability, including iterative test-group evaluations. We conclude with reflections on virtual reality's future capabilities in chemistry and education. Molecular Rift is open source and can be downloaded from GitHub.

  14. An ethnobotanical study of medicinal plants with narcotic, sedative and analgesic effects in west of Iran.

    Science.gov (United States)

    Saki, K; Bahmani, M; Rafieianb-Kopaei, M D; Asadollahi, K; Emaneini, M; Taherikalani, M

    2016-01-01

    The first step for identification of medicinal plants and their therapeutic effects is to determine their use by local people, traditional medicine books and personal experiences. The aim of this study was to document the medicinal plants used as analgesic, sedative or narcotic agents by local residents of Dehloran, Iran. Interviews conducted with 53 informants (38 male and 15 female) revealed that a total of 32 medicinal plants belonging to 22 families are used in Dehloran as narcotic, sedative and analgesic agents. The most utilized plant families were Asteraceae, Rosaceae and Fabaceae. Approximately 74% of the utilized plants was attributed to herbs, followed by trees (13%) and shrubs (13%). Sixty-six percent of the medicinal plants used in the study area were perennial and the rest were annual or biannual. The most widely used plant parts were flowers (34%) followed by leaves (24%) and fruits (14%). Thirty-nine percent of the medicinal plants were used as sedatives, 39% as analgesics, and 24% as narcotics. Recommended plants in this study can be good candidates for further clinical and laboratory trials on diseases that are associated with pain, suffering, stress and depression. They also can be used to develop new sedative, narcotic and analgesic drugs.

  15. NMR in structure-based drug design.

    Science.gov (United States)

    Carneiro, Marta G; Ab, Eiso; Theisgen, Stephan; Siegal, Gregg

    2017-11-08

    NMR spectroscopy is a powerful technique that can provide valuable structural information for drug discovery endeavors. Here, we discuss the strengths (and limitations) of NMR applications to structure-based drug discovery, highlighting the different levels of resolution and throughput obtainable. Additionally, the emerging field of paramagnetic NMR in drug discovery and recent developments in approaches to speed up and automate protein-observed NMR data collection and analysis are discussed. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  16. Organic carbamates in drug design and medicinal chemistry.

    Science.gov (United States)

    Ghosh, Arun K; Brindisi, Margherita

    2015-04-09

    The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug-target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent applications of carbamates in drug design and medicinal chemistry.

  17. "Not for human consumption": a review of emerging designer drugs.

    Science.gov (United States)

    Musselman, Megan E; Hampton, Jeremy P

    2014-07-01

    Synthetic, or "designer" drugs, are created by manipulating the chemical structures of other psychoactive drugs so that the resulting product is structurally similar but not identical to illegal psychoactive drugs. Originally developed in the 1960s as a way to evade existing drug laws, the use of designer drugs has increased dramatically over the past few years. These drugs are deceptively packaged as "research chemicals," "incense," "bath salts," or "plant food," among other names, with labels that may contain warnings such as "not for human consumption" or "not for sale to minors." The clinical effects of most new designer drugs can be described as either hallucinogenic, stimulant, or opioid-like. They may also have a combination of these effects due to designer side-chain substitutions. The easy accessibility and rapid emergence of new designer drugs have created challenges for health care providers when treating patients presenting with acute toxicity from these substances, many of which can produce significant and/or life-threatening adverse effects. Moreover, the health care provider has no way to verify the contents and/or potency of the agent ingested because it can vary between packages and distributors. Therefore, a thorough knowledge of the available designer drugs, common signs and symptoms of toxicity associated with these agents, and potential effective treatment modalities are essential to appropriately manage these patients. © 2014 Pharmacotherapy Publications, Inc.

  18. Multiscale Modeling in the Clinic: Drug Design and Development

    Energy Technology Data Exchange (ETDEWEB)

    Clancy, Colleen E.; An, Gary; Cannon, William R.; Liu, Yaling; May, Elebeoba E.; Ortoleva, Peter; Popel, Aleksander S.; Sluka, James P.; Su, Jing; Vicini, Paolo; Zhou, Xiaobo; Eckmann, David M.

    2016-02-17

    A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.

  19. Target based drug design - a reality in virtual sphere.

    Science.gov (United States)

    Verma, Saroj; Prabhakar, Yenamandra S

    2015-01-01

    The target based drug design approaches are a series of computational procedures, including visualization tools, to support the decision systems of drug design/discovery process. In the essence of biological targets shaping the potential lead/drug molecules, this review presents a comprehensive position of different components of target based drug design which include target identification, protein modeling, molecular dynamics simulations, binding/catalytic sites identification, docking, virtual screening, fragment based strategies, substructure treatment of targets in tackling drug resistance, in silico ADMET, structural vaccinology, etc along with the key issues involved therein and some well investigated case studies. The concepts and working of these procedures are critically discussed to arouse interest and to advance the drug research.

  20. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

    Directory of Open Access Journals (Sweden)

    Avinaba Mukherjee

    2016-03-01

    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

  1. Design and Synthesis of Epigenetic Drugs

    DEFF Research Database (Denmark)

    Leurs, Ulrike

    2014-01-01

    of histone- and DNA-modifying enzymes can lead to the development of diseases such as cancer. The histone demethylases of the KDM4 family have been implicated in a wide range of diseases, and are hence important drug targets. KDM4s belong to the bigger family of 2-OG oxygenases, an enzyme class sharing high...

  2. Personality Disorders, Narcotics, and Stimulants; Relationship in Iranian Male Substance Dependents Population

    OpenAIRE

    Noorbakhsh, Simasadat; Zeinodini, Zahra; Khanjani, Zeynab; Poorsharifi, Hamid; Rajezi Esfahani, Sepideh

    2015-01-01

    Background: Individuals with certain personality disorders, especially the antisocial and borderline personality disorders, are more prone to substance use disorders. Objectives: Regarding the importance of substance use disorders, this study aimed to explore the association between personality disorders and types of used drugs (narcotics and stimulants) in Iranian male substance users. Patients and Methods: The current study was a correlation study. We evaluated 285 male substance users and ...

  3. 4D-QSAR: Perspectives in Drug Design

    Directory of Open Access Journals (Sweden)

    Carolina H. Andrade

    2010-05-01

    Full Text Available Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. The quantitative structure–activity relationship (QSAR formalisms are among the most important strategies that can be applied for the successful design new molecules. This review provides a comprehensive review on the evolution and current status of 4D-QSAR, highlighting present challenges and new opportunities in drug design.

  4. Designer Drugs: A Review of Literature Abdulsallam Bakdash

    Directory of Open Access Journals (Sweden)

    Abdulsallam Bakdash

    2015-05-01

    Full Text Available A new phenomenon in the drug market has appeared in recent years: there has been an increase in the number and types of designer drugs. A massive influx of these structural and/or functional analogs of controlled substances has resulted in an increase in their marketing and abuse. At present, these drugs are significantly more widely available compared to previous years because they are relatively inexpensive and marketed as being safer than classic drugs of abuse. The most important factor in the spread of designer drugs is that the majority of these substances are undetectable as drugs or illegal drugs in standard drug testing procedures. The biological effects of these substances are largely unknown to both users and medical scientists. However, most known cases of abuse have shown serious and dangerous physical and psychological reactions in users. The manufacturing and marketing of designer drugs presents a major challenge for specialist sectors, especially laboratories that have to test these substances. This highlights the important role of drugcontrol institutions and regulatory and legislative bodies to determine the legal status of these drugs, which are designed and marketed - mostly through the internet - as being legal. All of these factors make it incumbent upon these sectors to form a unified goal and strategy to control these substances and prevent their spread. This review provides fundamental information about designer drugs. This will provide an accurate overview of their status, and will aid future work to develop a regulatory and legislative strategy to combat their manufacture, marketing, and use.

  5. Microcrystalline identification of selected designer drugs.

    Science.gov (United States)

    Elie, Leonie; Baron, Mark; Croxton, Ruth; Elie, Mathieu

    2012-01-10

    A microcrystalline test for the detection of 4-methylmethcathinone (mephedrone), benzylpiperazine (BZP) and 5,6-methylenedioxy-2-aminoindane (MDAI) using aqueous solutions of mercury chloride is described. Each of the compounds investigated formed specific drug-reagent crystals within minutes. The uniqueness of the test was confirmed by comparison of the microcrystalline response to that of other psychoactive stimulants and a common cutting agent. The limit of detection and cut-off levels for reference standards were established to 3 g/L and 5 g/L for mephedrone, 0.5 g/L for MDAI and 0.2 g/L and 0.3 g/L for BZP, respectively. Various mixtures of standards of either mephedrone, BZP or MDAI combined with caffeine were investigated for their microcrystalline response. Results showed that simultaneous detection of drug and cutting agent was possible with the concentrations tested but were dependant on the ratio of drug to cutting agent. BZP could be detected alongside caffeine from as low as 20% (v/v), MDAI from 40% (v/v) and mephedrone from 50% (v/v) and higher. Finally, seven samples of online purchased 'legal highs' were analysed using the developed test and the findings were compared to FTIR and GC-MS results. It was shown that 6 out of 7 samples did not contain the advertised active ingredient. Five samples consisted of BZP, caffeine and 1-[3-(trifluoromethyl)phenyl]piperazine (3-TFMPP). The microcrystalline tests carried out on these samples showed positive results for both BZP and caffeine without interference from other substances present. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Emergency Physicians' Knowledge of Cannabinoid Designer Drugs

    Directory of Open Access Journals (Sweden)

    Patrick M Lank

    2013-09-01

    Full Text Available Introduction: The use of synthetic drugs of abuse in the United States has grown in the last few years, with little information available on how much physicians know about these drugs and how they are treating patients using them. The objective of this study was to assess emergency physician (EP knowledge of synthetic cannabinoids (SC.Methods: A self-administered internet-based survey of resident and attending EPs at a large urban emergency department (ED was administered to assess familiarity with the terms Spice or K2 and basic knowledge of SC, and to describe some practice patterns when managing SC intoxication in the ED.Results: Of the 83 physicians invited to participate, 73 (88% completed surveys. The terms “Spice” and “K2” for SC were known to 25/73 (34% and 36/73 (49% of respondents. Knowledge of SC came most commonly (72% from non-medical sources, with lay publications and the internet providing most respondents with information. Among those with previous knowledge of synthetic cannabinoids, 25% were not aware that SC are synthetic drugs, and 17% did not know they are chemically most similar to marijuana. Among all participants, 80% felt unprepared caring for a patient in the ED who had used synthetic cannabinoids.Conclusion: Clinically active EPs are unfamiliar with synthetic cannabinoids. Even those who stated they had heard of synthetic cannabinoids answered poorly on basic knowledge questions. More education is needed among EPs of all ages and levels of training on synthetic cannabinoids. [West J Emerg Med. 2013;14(5:467–470.

  7. RECENT ADVANCES TOWARDS THE RATIONAL DESIGN OF PEPTIDE DRUGS

    OpenAIRE

    YEŞİLADA, Akgül; ÖZKANLI, Fügen

    2004-01-01

    In this review, after a short introduction to definition and physiological roles of regulatory peptides, problems faced during the development of peptide drugs, studies directed to solve these problems and rational design of peptide drugs with special emphesis on peptidomimetics are mentioned

  8. The Effectiveness of the Training of Problem-Solving and Decision-Making Skills on the Reduction of Addicts’ Positive Attitudes to Narcotics

    Directory of Open Access Journals (Sweden)

    Farxaneh Bahrami

    2013-05-01

    Full Text Available Aim: The purpose of this study was to examine the effect of the training of problem-solving and decision-making skills on the reduction of addicts’ positive attitudes to narcotics. Method: The design of this study was experimental design namely: pre and post test with control group. The population included all addicts referring to Sanandaj self-report centers (500 addicts. By random sampling, 60 addicts were selected and completed the attitude questionnaire to narcotics use. Each of experimental groups was under problem-solving and decision-making skills training for ten 90 minute sessions. No training given to control group. Results: After training, two experimental groups significantly had lower levels of positive attitude to narcotics use. No difference was observed between two experimental groups. Conclusion: The results of this study indicated that the training of problem-solving and decision-making skills can reduce the addicts’ positive attitudes to narcotics.

  9. Editorial: in silico drug design and medicinal chemistry).

    Science.gov (United States)

    Singla, Rajeev K

    2015-01-01

    Medicinal chemistry is not limited to molecules, their structures and design but also highly cohesive to pharmacological activities. The potency of a molecule varies by its structure. Hence structural activity relationship is the sub-branch which deals with the estimation of ability of a molecule in depicting any pharmacological activity. In silico drug design is a novel technique which is employed in designing a molecule by using computer aided software’s and bringing a superior and potent molecule. In recent years, in silico drug design has been merged with medicinal chemistry especially by the techniques like ligand based strategy to isolate the required structures. By such strategic techniques, there are high chances of delivering high throughput screening which involves of screening large number of molecules in a very less time. Involvement of such techniques would be a boon for development of new drug entity as it can aid in development of newer, safe, effective and potent drug molecules. Hence, the present issue is aimed to emphasize the cohesion between in silico drug design and it significance in medicinal chemistry. The articles which would be published will mainly focus on the role of in silico drug design techniques in the development of molecules to target various disease and disorders. Molecules can from natural/ synthetic/semi synthetic origin. Articles will be a treasure box consisting of employment of computational methods for unprecedented molecules. The issue will be sure an endorsement for international readership and researchers.

  10. Intratumor heterogeneity alters most effective drugs in designed combinations.

    Science.gov (United States)

    Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

    2014-07-22

    The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.

  11. The design of drugs for HIV and HCV.

    Science.gov (United States)

    De Clercq, Erik

    2007-12-01

    Since the discovery of the human immunodeficiency virus (HIV) in 1983, dramatic progress has been made in the development of novel antiviral drugs. The HIV epidemic fuelled the development of new antiviral drug classes, which are now combined to provide highly active antiretroviral therapies. The need for the treatment of hepatitis C virus (HCV), which was discovered in 1989, has also provided considerable impetus for the development of new classes of antiviral drugs, and future treatment strategies for chronic HCV might involve combination regimens that are analogous to those currently used for HIV. By considering the drug targets in the different stages of the life cycle of these two viruses, this article presents aspects of the history, medicinal chemistry and mechanisms of action of approved and investigational drugs for HIV and HCV, and highlights general lessons learned from anti-HIV-drug design that could be applied to HCV.

  12. Drug Use, the Drug Environment, and Child Physical Abuse and Neglect.

    Science.gov (United States)

    Freisthler, Bridget; Wolf, Jennifer Price; Wiegmann, Wendy; Kepple, Nancy J

    2017-08-01

    Although drug use is considered a risk factor for child maltreatment, very little work has examined how the drug environment may affect physical abuse and neglect by parents. Utilizing information from a telephone survey with 2,597 respondents from 43 cities with valid police data on narcotics incidents, we analyzed the relationship between drug use, drug availability, and child maltreatment using multilevel models. City-level rates of drug abuse and dependence were related to more frequent physical abuse. Parents who use drugs in areas with greater availability of drugs reported more physical abuse and physical neglect. Emotional support was protective of all types of maltreatment. While most child welfare interventions focus on reducing parental drug use in order to reduce child abuse, these findings suggest environmental prevention or neighborhood strengthening approaches designed to reduce the supply of illicit drugs may also reduce child abuse through multiple mechanisms.

  13. Counter Measures Criminal Act Of Narcotics

    Directory of Open Access Journals (Sweden)

    Mohammad Arief Amrullah

    2017-03-01

    Full Text Available Narcotics crimes that are part of organized crime are essentially one of crimes against development and crimes against social welfare that are central to national and international concerns and concerns. It is very reasonable, given the scope and dimensions so vast, that its activities contain features as organized crime, white-collar crime, corporate crime, and transnational crime. In fact, by means of technology can be one form of cyber crime. Based on such characteristics, the impacts and casualties are also very wide for the development and welfare of the community. It can even weaken national resilience.

  14. Design of an Implantable Device for Ocular Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jae-Hwan Lee

    2012-01-01

    Full Text Available Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD, diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics.

  15. Physics and Its Interfaces with Medicinal Chemistry and Drug Design

    Science.gov (United States)

    Santos, Ricardo N.; Andricopulo, Adriano D.

    2013-08-01

    Medicinal chemistry is a multidisciplinary subject that integrates knowledge from a variety of fields of science, including, but not limited to, chemistry, biology, and physics. The area of drug design involves the cooperative work of scientists with a diverse range of backgrounds and technical skills, trying to tackle complex problems using an integration of approaches and methods. One important contribution to this field comes from physics through studies that attempt to identify and quantify the molecular interactions between small molecules (drugs) and biological targets (receptors), such as the forces that govern the interactions, the thermodynamics of the drug-receptor interactions, and so on. In this context, the interfaces of physics, medicinal chemistry, and drug design are of vital importance for the development of drugs that not only have the right chemistry but also the right intermolecular properties to interact at the macromolecular level, providing useful information about the principles and molecular mechanisms underlying the therapeutic action of drugs. This article highlights some of the most important connections between physics and medicinal chemistry in the design of new drugs.

  16. Continued development of a portable widefield hyperspectral imaging (HSI) sensor for standoff detection of explosive, chemical, and narcotic residues

    Science.gov (United States)

    Nelson, Matthew P.; Gardner, Charles W.; Klueva, Oksana; Tomas, David

    2014-05-01

    Passive, standoff detection of chemical, explosive and narcotic threats employing widefield, shortwave infrared (SWIR) hyperspectral imaging (HSI) continues to gain acceptance in defense and security fields. A robust and user-friendly portable platform with such capabilities increases the effectiveness of locating and identifying threats while reducing risks to personnel. In 2013 ChemImage Sensor Systems (CISS) introduced Aperio, a handheld sensor, using real-time SWIR HSI for wide area surveillance and standoff detection of explosives, chemical threats, and narcotics. That SWIR HSI system employed a liquid-crystal tunable filter for real-time automated detection and display of threats. In these proceedings, we report on a next generation device called VeroVision™, which incorporates an improved optical design that enhances detection performance at greater standoff distances with increased sensitivity and detection speed. A tripod mounted sensor head unit (SHU) with an optional motorized pan-tilt unit (PTU) is available for precision pointing and sensor stabilization. This option supports longer standoff range applications which are often seen at checkpoint vehicle inspection where speed and precision is necessary. Basic software has been extended to include advanced algorithms providing multi-target display functionality, automatic threshold determination, and an automated detection recipe capability for expanding the library as new threats emerge. In these proceedings, we report on the improvements associated with the next generation portable widefield SWIR HSI sensor, VeroVision™. Test data collected during development are presented in this report which supports the targeted applications for use of VeroVision™ for screening residue and bulk levels of explosive and drugs on vehicles and personnel at checkpoints as well as various applications for other secure areas. Additionally, we highlight a forensic application of the technology for assisting forensic

  17. MPD3: a useful medicinal plants database for drug designing.

    Science.gov (United States)

    Mumtaz, Arooj; Ashfaq, Usman Ali; Ul Qamar, Muhammad Tahir; Anwar, Farooq; Gulzar, Faisal; Ali, Muhammad Amjad; Saari, Nazamid; Pervez, Muhammad Tariq

    2017-06-01

    Medicinal plants are the main natural pools for the discovery and development of new drugs. In the modern era of computer-aided drug designing (CADD), there is need of prompt efforts to design and construct useful database management system that allows proper data storage, retrieval and management with user-friendly interface. An inclusive database having information about classification, activity and ready-to-dock library of medicinal plant's phytochemicals is therefore required to assist the researchers in the field of CADD. The present work was designed to merge activities of phytochemicals from medicinal plants, their targets and literature references into a single comprehensive database named as Medicinal Plants Database for Drug Designing (MPD3). The newly designed online and downloadable MPD3 contains information about more than 5000 phytochemicals from around 1000 medicinal plants with 80 different activities, more than 900 literature references and 200 plus targets. The designed database is deemed to be very useful for the researchers who are engaged in medicinal plants research, CADD and drug discovery/development with ease of operation and increased efficiency. The designed MPD3 is a comprehensive database which provides most of the information related to the medicinal plants at a single platform. MPD3 is freely available at: http://bioinform.info .

  18. Assessment of the Impact of the Narcotics Market on the Regional Socio-Economic Development

    Directory of Open Access Journals (Sweden)

    Aleksey Nikolaevich Klevakin

    2018-03-01

    Full Text Available The article considers the market of narcotics as a part of the formal and informal economy. By narcotics, the author means psychoactive substances and plants containing them, which are banned, subject to control or non-prohibited, but have a psychophysical effect on human body. Drug-related psychoactive substances are classified according to the prohibition criterion and restrictions on a turnover with reference to the illegal (criminal or shadow economy. The author considers the illegal drug market as a latent self-organizing system of socio-economic relations of criminal and shadow nature. Such market is oriented towards the turnover of potentially illegal or dangerous psychoactive substances, which are prohibited or restricted for use in non-medical purposes. The analysis of the state and development of the drug situation on the territory of the entities of the Ural Federal District confirms the relevance of the problem of drug abuse. In recent years, the primary incidence of drug addiction and harmful drug use among the adolescents aged 15–17 have grown. Synthetic narcotics and psychotropic substances of high narcogenicity dominate in the current drug market. Over the past 5 years, the average cost of a single dose of drug remains virtually unchanged. This reflects the conditional balance of purchasing power and competition in the drug market. The disparity in the volume of seized cannabis drugs and the number of cannabinoid users observed by medical institutions suggests a high level of latency in this category of drug users. To assess the degree of negative impact of the drug market, the author proposes to use a method of calculating the socioeconomic costs of the consequences of drug addiction. The methodology is supplemented with tools for determining the number of psychoactive substances consumers on the basis of the mass of these substances withdrawn from illicit trafficking, using the concentration and recalculation coefficients

  19. Trace Contraband Detection Field-Test by the South Texas Specialized Crimes and Narcotics Task Force

    Energy Technology Data Exchange (ETDEWEB)

    Hannum, David W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Contraband Detection Dept.; Shannon, Gary W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Contraband Detection Dept.

    2006-04-01

    This report describes the collaboration between the South Texas Specialized Crimes and Narcotics Task Force (STSCNTF) and Sandia National Laboratories (SNL) in a field test that provided prototype hand-held trace detection technology for use in counter-drug operations. The National Institute of Justice (NIJ)/National Law Enforcement and Corrections Technology Center (NLECTC)/Border Research and Technology Center (BRTC) was contacted by STSCNTF for assistance in obtaining cutting-edge technology. The BRTC created a pilot project for Sandia National Laboratories (SNL) and the STSCNTF for the use of SNL’s Hound, a hand-held sample collection and preconcentration system that, when combined with a commercial chemical detector, can be used for the trace detection of illicit drugs and explosives. The STSCNTF operates in an area of high narcotics trafficking where methods of concealment make the detection of narcotics challenging. Sandia National Laboratories’ (SNL) Contraband Detection Department personnel provided the Hound system hardware and operational training. The Hound system combines the GE VaporTracer2, a hand-held commercial chemical detector, with an SNL-developed sample collection and preconcentration system. The South Texas Task force reported a variety of successes, including identification of a major shipment of methamphetamines, the discovery of hidden compartments in vehicles that contained illegal drugs and currency used in drug deals, and the identification of a suspect in a nightclub shooting. The main advantage of the hand-held trace detection unit is its ability to quickly identify the type of chemical (drugs or explosives) without a long lag time for laboratory analysis, which is the most common analysis method for current law enforcement procedures.

  20. Comparison between narcotic 'receptors' in the guinea-pig ileum and the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Terenius, L [Uppsala Univ. (Sweden)

    1975-01-01

    The receptors, i.e., specific binding molecules, for narcotic analgesics in the guinea-pig ileum and rat brain have been compared. The relative affinities of a number of narcotics for the two receptors were very similar and discrimination between stereoisomeric agents was identical. The dissociation constants for dihydromorphine binding were 0.78 nM for the ileum and 1.4 nM for the brain receptor, respectively. There was a good correspondance between receptor affinities on the ileum preparation and the literature data on biologic activity on the isolated ileum. Codeine, diphenoxylate, difenoxine and loperamide, which are used clinically for the treatment of diarrhoea showed no selectivity against the ileum receptor. The two latter drugs had a very high receptor affinity and their lack of narcotic activity after oral administration is probably attributable to lack of penetration of the CNS. Receptor binding in both ileum and brain preparations was inhibited by N-ethylmaleimide, Triton X-100, trypsin and phospholipase C. There were small quantitative differences in sensitivity to these agents but it is difficult to assess whether this is because of real differences between the receptor molecules or attributable to secondary effects. As previously described for the brain receptor, the ileum receptor appeared to be present in a fraction enriched in plasma membranes.

  1. 76 FR 40306 - Harmonizing Schedule I Drug Requirements

    Science.gov (United States)

    2011-07-08

    ... an amphetamine, narcotic, or any habit-forming drug, are not medically qualified to operate a... of the 1984 Act also grants the Secretary broad power in carrying out motor carrier safety statutes...: Controlled substances on the DEA Schedule I, amphetamines, narcotics, or other habit-forming drugs. Section...

  2. 77 FR 4479 - Harmonizing Schedule I Drug Requirements

    Science.gov (United States)

    2012-01-30

    ..., narcotic, or any habit-forming drug, are not medically qualified to operate a commercial motor vehicle... grants the Secretary broad power in carrying out motor carrier safety statutes and regulations to..., amphetamines, narcotics, or other habit-forming drugs. Section 391.41(b)(12)(ii) contained an exception for a...

  3. Drug Enforcement Administration.

    Science.gov (United States)

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  4. Designing an intuitive web application for drug discovery scientists.

    Science.gov (United States)

    Karamanis, Nikiforos; Pignatelli, Miguel; Carvalho-Silva, Denise; Rowland, Francis; Cham, Jennifer A; Dunham, Ian

    2018-01-11

    We discuss how we designed the Open Targets Platform (www.targetvalidation.org), an intuitive application for bench scientists working in early drug discovery. To meet the needs of our users, we applied lean user experience (UX) design methods: we started engaging with users very early and carried out research, design and evaluation activities within an iterative development process. We also emphasize the collaborative nature of applying lean UX design, which we believe is a foundation for success in this and many other scientific projects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Connecting drug delivery reality to smart materials design.

    Science.gov (United States)

    Grainger, David W

    2013-09-15

    Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Drug design and discovery: translational biomedical science varies among countries.

    Science.gov (United States)

    Weaver, Ian N; Weaver, Donald F

    2013-10-01

    Drug design and discovery is an innovation process that translates the outcomes of fundamental biomedical research into therapeutics that are ultimately made available to people with medical disorders in many countries throughout the world. To identify which nations succeed, exceed, or fail at the drug design/discovery endeavor--more specifically, which countries, within the context of their national size and wealth, are "pulling their weight" when it comes to developing medications targeting the myriad of diseases that afflict humankind--we compiled and analyzed a comprehensive survey of all new drugs (small molecular entities and biologics) approved annually throughout the world over the 20-year period from 1991 to 2010. Based upon this analysis, we have devised prediction algorithms to ascertain which countries are successful (or not) in contributing to the worldwide need for effective new therapeutics. © 2013 Wiley Periodicals, Inc.

  7. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    Science.gov (United States)

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  8. A Prospective Method to Guide Small Molecule Drug Design

    Science.gov (United States)

    Johnson, Alan T.

    2015-01-01

    At present, small molecule drug design follows a retrospective path when considering what analogs are to be made around a current hit or lead molecule with the focus often on identifying a compound with higher intrinsic potency. What this approach overlooks is the simultaneous need to also improve the physicochemical (PC) and pharmacokinetic (PK)…

  9. Design of new polymeric formulations for drug nanocarriers

    Science.gov (United States)

    Mattu, C.; Li, R.; Sartori, S.; Boffito, M.; Ramtoola, Z.; Ciardelli, G.

    2012-07-01

    In this work, novel strategies for the design and characterization of complex nanosized drug delivery systems for the release of different formulations were proposed and investigated. Natural or synthetic polymers, such as chitosan, poly (D,L lactide) (PLA) and proprietary polyesterurethanes, were used to prepare carriers for different applications in nanomedicine.

  10. The evolution of drug design at Merck Research Laboratories.

    Science.gov (United States)

    Brown, Frank K; Sherer, Edward C; Johnson, Scott A; Holloway, M Katharine; Sherborne, Bradley S

    2017-03-01

    On October 5, 1981, Fortune magazine published a cover article entitled the "Next Industrial Revolution: Designing Drugs by Computer at Merck". With a 40+ year investment, we have been in the drug design business longer than most. During its history, the Merck drug design group has had several names, but it has always been in the "design" business, with the ultimate goal to provide an actionable hypothesis that could be tested experimentally. Often the result was a small molecule but it could just as easily be a peptide, biologic, predictive model, reaction, process, etc. To this end, the concept of design is now front and center in all aspects of discovery, safety assessment and early clinical development. At present, the Merck design group includes computational chemistry, protein structure determination, and cheminformatics. By bringing these groups together under one umbrella, we were able to align activities and capabilities across multiple research sites and departments. This alignment from 2010 to 2016 resulted in an 80% expansion in the size of the department, reflecting the increase in impact due to a significant emphasis across the organization to "design first" along the entire drug discovery path from lead identification (LID) to first in human (FIH) dosing. One of the major advantages of this alignment has been the ability to access all of the data and create an adaptive approach to the overall LID to FIH pathway for any modality, significantly increasing the quality of candidates and their probability of success. In this perspective, we will discuss how we crafted a new strategy, defined the appropriate phenotype for group members, developed the right skillsets, and identified metrics for success in order to drive continuous improvement. We will not focus on the tactical implementation, only giving specific examples as appropriate.

  11. The evolution of drug design at Merck Research Laboratories

    Science.gov (United States)

    Brown, Frank K.; Sherer, Edward C.; Johnson, Scott A.; Holloway, M. Katharine; Sherborne, Bradley S.

    2017-03-01

    On October 5, 1981, Fortune magazine published a cover article entitled the "Next Industrial Revolution: Designing Drugs by Computer at Merck". With a 40+ year investment, we have been in the drug design business longer than most. During its history, the Merck drug design group has had several names, but it has always been in the "design" business, with the ultimate goal to provide an actionable hypothesis that could be tested experimentally. Often the result was a small molecule but it could just as easily be a peptide, biologic, predictive model, reaction, process, etc. To this end, the concept of design is now front and center in all aspects of discovery, safety assessment and early clinical development. At present, the Merck design group includes computational chemistry, protein structure determination, and cheminformatics. By bringing these groups together under one umbrella, we were able to align activities and capabilities across multiple research sites and departments. This alignment from 2010 to 2016 resulted in an 80% expansion in the size of the department, reflecting the increase in impact due to a significant emphasis across the organization to "design first" along the entire drug discovery path from lead identification (LID) to first in human (FIH) dosing. One of the major advantages of this alignment has been the ability to access all of the data and create an adaptive approach to the overall LID to FIH pathway for any modality, significantly increasing the quality of candidates and their probability of success. In this perspective, we will discuss how we crafted a new strategy, defined the appropriate phenotype for group members, developed the right skillsets, and identified metrics for success in order to drive continuous improvement. We will not focus on the tactical implementation, only giving specific examples as appropriate.

  12. [Effects of the new comprehensive system for designating illegal drug components on the abuse of designer drugs and future problems based on an online questionnaire].

    Science.gov (United States)

    Morino, Taichi; Okazaki, Mitsuhiro; Toda, Takaki; Yokoyama, Takashi

    2015-12-01

    Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future.

  13. Generative Recurrent Networks for De Novo Drug Design.

    Science.gov (United States)

    Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

    2018-01-01

    Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  14. Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

    Science.gov (United States)

    Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

    2011-02-01

    The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

  15. 76 FR 44613 - Designation of Eight Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2011-07-26

    ... OFFICE OF NATIONAL DRUG CONTROL POLICY Designation of Eight Counties as High Intensity Drug Trafficking Areas AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy has designated eight additional counties as High Intensity Drug...

  16. Computer-aided drug design at Boehringer Ingelheim

    Science.gov (United States)

    Muegge, Ingo; Bergner, Andreas; Kriegl, Jan M.

    2017-03-01

    Computer-Aided Drug Design (CADD) is an integral part of the drug discovery endeavor at Boehringer Ingelheim (BI). CADD contributes to the evaluation of new therapeutic concepts, identifies small molecule starting points for drug discovery, and develops strategies for optimizing hit and lead compounds. The CADD scientists at BI benefit from the global use and development of both software platforms and computational services. A number of computational techniques developed in-house have significantly changed the way early drug discovery is carried out at BI. In particular, virtual screening in vast chemical spaces, which can be accessed by combinatorial chemistry, has added a new option for the identification of hits in many projects. Recently, a new framework has been implemented allowing fast, interactive predictions of relevant on and off target endpoints and other optimization parameters. In addition to the introduction of this new framework at BI, CADD has been focusing on the enablement of medicinal chemists to independently perform an increasing amount of molecular modeling and design work. This is made possible through the deployment of MOE as a global modeling platform, allowing computational and medicinal chemists to freely share ideas and modeling results. Furthermore, a central communication layer called the computational chemistry framework provides broad access to predictive models and other computational services.

  17. Web-based services for drug design and discovery.

    Science.gov (United States)

    Frey, Jeremy G; Bird, Colin L

    2011-09-01

    Reviews of the development of drug discovery through the 20(th) century recognised the importance of chemistry and increasingly bioinformatics, but had relatively little to say about the importance of computing and networked computing in particular. However, the design and discovery of new drugs is arguably the most significant single application of bioinformatics and cheminformatics to have benefitted from the increases in the range and power of the computational techniques since the emergence of the World Wide Web, commonly now referred to as simply 'the Web'. Web services have enabled researchers to access shared resources and to deploy standardized calculations in their search for new drugs. This article first considers the fundamental principles of Web services and workflows, and then explores the facilities and resources that have evolved to meet the specific needs of chem- and bio-informatics. This strategy leads to a more detailed examination of the basic components that characterise molecules and the essential predictive techniques, followed by a discussion of the emerging networked services that transcend the basic provisions, and the growing trend towards embracing modern techniques, in particular the Semantic Web. In the opinion of the authors, the issues that require community action are: increasing the amount of chemical data available for open access; validating the data as provided; and developing more efficient links between the worlds of cheminformatics and bioinformatics. The goal is to create ever better drug design services.

  18. Closed to reason: time for accountability for the International Narcotic Control Board

    Directory of Open Access Journals (Sweden)

    Small Dan

    2007-05-01

    Full Text Available Abstract For more than two decades, the International Narcotic Control Board (INCB has tried to stop harm reduction and its HIV prevention programs. This posture is based on a fundamental misunderstanding of their responsibilities and of drug addiction itself – i.e. as a public health and clinical care matter made criminal by decree. A recent focal point for the Board's action has been rejecting the use of supervised injection facilities to reduce morbidity and mortality of drug injectors. They single out individual countries and attempt to bully them into rejecting such programs under the banner of the United Nations (falsely and in the name of international treaties. Their unrelenting and unjustified badgering of signatories to the international treaties that established the INCB is not only unjustified; it is an affront to one of the core purposes of the Board itself: to ensure adequate medical supplies and safe use of controlled substances. The INCB's ill-conceived obsession with intravenousaddiction as a crime flies in the face of the medical view and policies of the World Health Organization and the universally endorsed principles of the General Assembly of the United Nations. The latest target of the INCB is North America's only supervised injection facility, Insite, located in the inner city of Vancouver, Canada. Using the power of their office to meddle in matters of public health for individual nations is without medical, scientific or legal justification. But, most importantly, it is a matter of lifeand death for these most marginalized of citizens. The empirical evidence remains that a significant portion of the continued growth of the AIDS pandemic is due to injecting drug use, and the INCB's intrusion will inevitably result in additional deaths due to preventable HIV infections and drug overdoses. So we are very pleased to call to our readers' attention to a recent report produced by the Canadian HIV/AIDS Legal Network and the

  19. Psychiatric aspects of designer drugs and new psychoactive substances consumption

    Directory of Open Access Journals (Sweden)

    Antsyborov A.V.

    2017-02-01

    Full Text Available according to the authors, appeared not long ago new psychoactive substances (designer drugs, including synthetic cannabinoids, derivatives of cathinone, phenethylamines, new stimulants, synthetic opioids, tryptamine derivatives, phencyclidine, piperazine, agonists of GABA (A/B receptors have become a serious problem for both consumers and doctors. Consumers of these substances are attracted primarily by the intensity of psychoactive effects, as well as «legal purity», which is declared by shadow producers. This indicates that there are some significant difficulties of laboratory typing of new surfactants. Designer drugs when ingested, can affect a range of neurotransmitter pathways/receptors: dopamine, cannabinoid (CB1, GABA(A/B, 5-HT2A, glutamate, and k-opioid receptors (KOR, the imbalance of which leads to the development of polymorphic psychotic disorders.

  20. 21 CFR 516.29 - Termination of MUMS-drug designation.

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.29 Termination of MUMS-drug designation. (a... exclusive marketing rights under this subpart. (d) FDA may terminate designation if it independently...

  1. 78 FR 22620 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-04-16

    ...''), Col Bella Vista, Casa No. 09, Camino a Rotulo de Coca Cola, San Pedro Sula, Cortes, Honduras; DOB 14...] (Linked To: AUTO PARTES HANDAL S. DE R.L. DE C.V.; Linked To: RANCHO LA HERRADURA; Linked To: SUPERTIENDAS..., La Ceiba, Atlantida, Honduras; Ave Junior, Entre 7 y 6 Calle Sureste, San Pedero Sula, Cortes...

  2. 77 FR 838 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-01-06

    ... & EXPORT, S.A. (GTI); c/o MICRO EMPRESA ASHQUI; DOB 9 Jan 1971; alt. DOB 9 Jan 1970; POB Ghobeiri, Lebanon..., Panama; Edificio Servicios Aeroportuarios, Segundo Piso, Local 12, Panama City, Panama; RUC 1652278-1... 18 Norte, No. 3N-24, Oficina 602, Cali, Colombia; NIT 9000420320 (Colombia) [SDNTK]. 33. MICRO...

  3. 76 FR 10668 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-02-25

    ... Administration, the Secretary of Defense, the Secretary of State, and the Secretary of Homeland Security when... are found to be: (1) Materially assisting in, or providing financial or technological support for or....k.a. AZIMI, Haji Muhammad Rafi; a.k.a. RAFI, Abdul); DOB 15 Feb 1972; POB Afghanistan; citizen...

  4. 75 FR 36474 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-06-25

    ... Administration, the Secretary of Defense, the Secretary of State, and the Secretary of Homeland Security when... are found to be: (1) Materially assisting in, or providing financial or technological support for or...: Individuals: 1. SOLARTE CERON, Olidem Romel (a.k.a. SOLARTE CERON, Oliver); Colombia; DOB 05 Feb 1971; Citizen...

  5. 75 FR 14255 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-03-24

    ... Administration, the Secretary of Defense, the Secretary of State, and the Secretary of Homeland Security when... are found to be: (1) Materially assisting in, or providing financial or technological support for or...; Citizen Colombia; Nationality Colombia; Cedula No. 15349556 (Colombia); (INDIVIDUAL) [SDNTK] 2. USUGA...

  6. 75 FR 10557 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-03-08

    ... BUSTOS ARIZA Y CIA. S.C.S., Bogota, Colombia; c/o MODERNA EXPRESS TRANSPORTE DE CARGA LTDA., Bogota..., Colombia; c/o LOGISTICA Y TRANSPORTE NORVAL LTDA., Bogota, Colombia; Calle 135 No. 17-25 apto. 503, Bogota.... LOGISTICA Y TRANSPORTE NORVAL LTDA., Avenida Boyaca No. 68-24, Bogota, Colombia; NIT 900224846-0 (Colombia...

  7. 77 FR 48609 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-08-14

    ... in, or providing financial or technological support for or to, or providing goods or services in... service at (202) 622-0077. Background The Kingpin Act became law on December 3, 1999. The Kingpin Act...; 10/12 Halfmoon Avenue, Belmopan City, Belize; Tax ID No. GST- SIG 000465 (Belize) [SDNTK]. 2. CROWN...

  8. 77 FR 23807 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-04-20

    .... DE C.V.; c/o TECNOLOGIA OPTIMA CORPORATIVA S. DE R.L. DE C.V.; Paseo de los Heroes 108-104, Tijuana...; Folio Mercantil No. 13537 (Mexico); R.F.C. SFO011205UJ8 (Mexico) [SDNTK] TECNOLOGIA OPTIMA CORPORATIVA S...

  9. 76 FR 6843 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-02-08

    ..., Jaslico, Mexico; Vereda Del Canario 1, Guadalajara, Jalisco, Mexico; Puerto de Hierro, Zapopan, Jalisco..., Jalisco, Mexico; Puerto de Hierro, Zapopan, Jalisco, Mexico; Mexico City, Distrito Federal, Mexico.... RODRIGUEZ OLIVERA, Daniel (a.k.a. RODRIGUEZ MORFIN, Daniel), Puerto de Hierro, Zapopan, Jalisco, Mexico...

  10. 78 FR 61000 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-10-02

    ...; Puerto de Hierro, Zapopan, Jalisco, Mexico; Fresno, CA; DOB 3 Apr 1972; alt. DOB 1960; alt. DOB 1966; POB..., Jaslico, Mexico; Vereda Del Canario 1, Guadalajara, Jalisco, Mexico; Puerto de Hierro, Zapopan, Jalisco...

  11. 77 FR 51616 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-08-24

    ..., Condominio La Laguna, Casa 1, Guatemala, Guatemala; Registration ID 388175 (Guatemala) [SDNTK]. 5. AUTO HOTEL... Villa Bodega 23, Guatemala City, Guatemala; Registration ID 71152 (Guatemala) [SDNTK]. 7. BOUTIQUE...

  12. 77 FR 61051 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-10-05

    ..., Distrito Federal Codigo Postal 03020, Mexico; Calle Sor Juana Ines de la Cruz No. 144, Departamento 124... (Mexico) (individual) [SDNTK]. 2. FELIX FELIX, Victor Manuel (a.k.a. CASTRO RODRIGUEZ, Raul), Callejon...

  13. 77 FR 58912 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-09-24

    ...(b) of the Kingpin Act. Individual: 1. LOPEZ PERDIGON, Roberto Manuel; DOB 09 Sep 1971; POB Caracas... Cruz, Venezuela; RIF J-31327555-7 (Venezuela) [SDNTK]. Dated: September 13, 2012. Adam J. Szubin...

  14. 75 FR 65554 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-10-25

    ... objective of denying their businesses and agents access to the U.S. financial system and to the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin Act blocks all property and... with the Attorney General, the Director of the Central Intelligence Agency, the Director of the Federal...

  15. 78 FR 13760 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-02-28

    ... denying their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin Act blocks all property and interests in... General, the Director of the Central Intelligence Agency, the Director of the Federal Bureau of...

  16. 75 FR 44311 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-07-28

    ... their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin Act blocks all property and interests in..., the Director of the Central Intelligence Agency, the Director of the Federal Bureau of Investigation...

  17. 76 FR 56875 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-09-14

    ... basis, with the objective of denying their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin Act... Treasury in consultation with the Attorney General, the Director of the Central Intelligence Agency, the...

  18. 76 FR 5857 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-02-02

    ... objective of denying their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin Act blocks all property and... Attorney General, the Director of the Central Intelligence Agency, the Director of the Federal Bureau of...

  19. 75 FR 20425 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-04-19

    ... their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin Act blocks all property and interests in..., the Director of the Central Intelligence Agency, the Director of the Federal Bureau of Investigation...

  20. 77 FR 29755 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-05-18

    ... denying their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The Kingpin Act blocks all property and interests in... General, the Director of the Central Intelligence Agency, the Director of the Federal Bureau of...

  1. 77 FR 39573 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-07-03

    ... traffickers and their organizations on a worldwide basis, with the objective of denying their businesses and.... companies and individuals. The Kingpin Act blocks all property and interests in property, subject to U.S... of the Central Intelligence Agency, the Director of the Federal Bureau of Investigation, the...

  2. 77 FR 4400 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-01-27

    ... organizations on a worldwide basis, with the objective of denying their businesses and agents access to the U.S. financial system and the benefits of trade and transactions involving U.S. companies and individuals. The... Central Intelligence Agency, the Director of the Federal Bureau of Investigation, the Administrator of the...

  3. 76 FR 25407 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-05-04

    ... their organizations on a worldwide basis with the objective of denying their businesses and agents.... companies and individuals. The Kingpin Act blocks all property and interests in property, subject to U.S... of the Central Intelligence Agency, the Director of the Federal Bureau of Investigation, the...

  4. 77 FR 56271 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-09-12

    ... identified by the President. In addition, the Secretary of the Treasury, in consultation with the Attorney..., Fraccionamiento Colinas de San Miguel, Culiacan, Sinaloa, Mexico; DOB 19 Aug 1959; alt. DOB 30 Dec 1966; POB Sinaloa, Mexico; nationality Mexico; citizen Mexico; C.U.R.P. LOPG590819MSLPRR04 (Mexico); alt. C.U.R.P...

  5. 75 FR 34214 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-06-16

    ... organizations on a worldwide basis. It provides a statutory framework for the President to impose sanctions... traffickers as identified by the President. In addition, the Secretary of the Treasury consults with the... Italia, Michoac[aacute]n, Mexico; Calle Articulo 123 Numero 103, Colonia Centro, Nueva Italia, Michoac...

  6. 78 FR 29814 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-05-21

    ... identified by the President. In addition, the Secretary of the Treasury, in consultation with the Attorney..., Ciudad Acuna, Coahuila, Mexico; DOB 30 Dec 1973; POB Ciudad Acuna, Coahuila, Mexico; alt. POB Coahuila, Mexico; nationality Mexico; citizen Mexico; C.U.R.P. AAPA731230HCLNRL07 (Mexico) (individual) [SDNTK...

  7. 78 FR 3083 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-01-15

    ... identified by the President. In addition, the Secretary of the Treasury, in consultation with the Attorney... 80220, Mexico; Calle Escobedo No. 24, Localidad El Dorado, Culiacan, Sinaloa 80450, Mexico; DOB 22 Feb 1966; POB Culiacan, Sinaloa, Mexico; nationality Mexico; citizen Mexico; R.F.C. LOND6602221Y5 (Mexico...

  8. 76 FR 67792 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-11-02

    ... organizations on a worldwide basis. It provides a statutory framework for the President to impose sanctions... traffickers as identified by the President. In addition, the Secretary of the Treasury consults with the... Costa Bella, Ensenada, Baja California, Mexico; (ENTITY) [SDNTK] 2. AUTODROMO CULIACAN RACE PARK, Blvd...

  9. 77 FR 28670 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-05-15

    ... identified by the President. In addition, the Secretary of the Treasury, in consultation with the Attorney... SALAZAR, Ivan Archibaldo); Mexico; DOB 02 Oct 1980; POB Sinaloa, Mexico; Citizen Mexico; Nationality Mexico; (INDIVIDUAL) [SDNTK] 2. GUZMAN LOPEZ, Ovidio, Mexico; DOB 29 Mar 1990; POB Sinaloa, Mexico...

  10. 77 FR 36041 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-06-15

    ... identified by the President. In addition, the Secretary of the Treasury, in consultation with the Attorney.... 222, Colonia Ciudad del Sol, Zapopan, Jalisco 45050, Mexico; Calle Quebec 606 B, Prados Providencia, Guadalajara, Jalisco, Mexico; Calle Mango 2129, Colonia Paraisos del Colli, Guadalajara, Jalisco, Mexico...

  11. 77 FR 2347 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-01-17

    ... identified by the President. In addition, the Secretary of the Treasury, in consultation with the Attorney.... 80010, Mexico; Boulevard Universitarios No. 789, Local 4, Colonia Villa Universidad, Culiacan, Sinaloa C.P. 80010, Mexico; Localidad San Jose del Barranco S/N, Badiraguato, Sinaloa C.P. 80500, Mexico; DOB...

  12. 78 FR 59766 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-09-27

    ... Esteban, Olancho, Honduras; Numero de Identidad 1517-1950-00095 (Honduras) (individual) [SDNTK]. 3. RIVERA... Identidad 0209-1949-00019 (Honduras) (individual) [SDNTK]. 4. RIVERA MARADIAGA, Javier Eriberto (a.k.a..., Casa 234, Tocoa, Colon, Honduras; DOB 20 Apr 1972; POB Tocoa, Colon, Honduras; Numero de Identidad 0209...

  13. 75 FR 15772 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-03-30

    .... OEGI740531 (Mexico); Electoral Registry No. ORGLIS740531121H100 (Mexico); (INDIVIDUAL) [SDNTK] 29. VERA CALVA, Carlos, Calle E. Zapata No. 2, Col. Plan de Ayala, Tihuatlan, Veracruz, Mexico; DOB 10 Jul 1970; POB Poza...

  14. 76 FR 25406 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-05-04

    ...; Calle Comercio No. 50, Colonia Escandon, Delegacion Miguel Hidalgo, Mexico City, Distrito Federal C.P. 11800, Mexico; Calle Milpa No. 87, Colonia El Vigia, Zapopan, Jalisco C.P. 45100, Mexico; Calle...

  15. 77 FR 44715 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-07-30

    ..., S.A. DE C.V. (a.k.a. LA TIJERA PARQUE INDUSTRIAL; a.k.a. PROVENZA CENTER), Av. Adolfo Lopez Mateos... (Mexico) [SDNTK]. 8. PETROBARRANCOS, S.A. DE C.V., Av. Benjamin Hill No. 5602, Col. Industrial el Palmito...

  16. 78 FR 66990 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-11-07

    ..., Zapopan, Jalisco C.P. 45129, Mexico; Paseo de los Parques No. 3995, Interior 7, Zapopan, Jalisco C.P.... 45129, Mexico; Paseo de los Parques No. 3995, Interior 7, Zapopan, Jalisco C.P. 45110, Mexico; Loreto...

  17. 76 FR 59483 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-09-26

    ... AMAZONICOS S.A.S., Bogota, Colombia; c/o PARQUES TEMATICOS S.A.S., Medellin, Colombia; c/o PROMO RAIZ S.A.S..., Distrito Federal, Mexico; c/o PARQUES TEMATICOS S.A., Medellin, Colombia; c/o PROMO RAIZ S.A., Medellin... 16 Sur No. 46A-49 Piso 6, Medellin, Colombia; NIT 800220730-4 (Colombia) [SDNTK] 7. PARQUES TEMATICOS...

  18. 76 FR 11561 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2011-03-02

    ....A., Cali, Colombia; c/o INVERSIONES CIFUENTES Y CIA. S. EN C., Medellin, Colombia; c/o PARQUES... Federal, Mexico; c/o LINEA AEREA PUEBLOS AMAZONICOS S.A.S., Bogota, Colombia; c/o PARQUES TEMATICOS S.A... HOTELES Y BIENES S.A., Bogota, Colombia; c/o INVERPUNTO DEL VALLE S.A., Cali, Colombia; c/o PARQUES...

  19. 78 FR 36635 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2013-06-18

    ..., Mexico; Paseo de los Parques No. 3995, Interior 7, Zapopan, Jalisco C.P. 45110, Mexico; Loreto Mendez...) (individual) [SDNTK]. 11. RIEBELING CORDERO, Hilda, 3888 Calle Paseo de los Parques, Colonia Colinas de San...

  20. 75 FR 64782 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-10-20

    ... Negros, Baja California Norte, Mexico; R.F.C. CDO-980604-4V7 (Mexico); (ENTITY) [SDNTK]. 4. MANTENIMIENTO.... FLCCAL64032609H300 (Mexico); (INDIVIDUAL) [SDNTK]. 2. GARCIA SANCHEZ, Ricardo, c/o MANTENIMIENTO, AERONAUTICA...

  1. 75 FR 79440 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2010-12-20

    ..., Colombia; c/o FERTILIZANTES LIQUIDOS DE LA SABANA LTDA., Bogota, Colombia; Calle 109 No. 21-41 Apto. 403...) [SDNTK] 13. FERTILIZANTES LIQUIDOS DE LA SABANA LTDA. (a.k.a. FERTILISA LTDA.), Calle 98 Bis No. 57-66...

  2. Design of diversity and focused combinatorial libraries in drug discovery.

    Science.gov (United States)

    Young, S Stanley; Ge, Nanxiang

    2004-05-01

    Using well-characterized chemical reactions and readily available monomers, chemists are able to create sets of compounds, termed libraries, which are useful in drug discovery processes. The design of combinatorial chemical libraries can be complex and there has been much information recently published offering suggestions on how the design process can be carried out. This review focuses on literature with the goal of organizing current thinking. At this point in time, it is clear that benchmarking of current suggested methods is required as opposed to further new methods.

  3. Fragment-based drug discovery and molecular docking in drug design.

    Science.gov (United States)

    Wang, Tao; Wu, Mian-Bin; Chen, Zheng-Jie; Chen, Hua; Lin, Jian-Ping; Yang, Li-Rong

    2015-01-01

    Fragment-based drug discovery (FBDD) has caused a revolution in the process of drug discovery and design, with many FBDD leads being developed into clinical trials or approved in the past few years. Compared with traditional high-throughput screening, it displays obvious advantages such as efficiently covering chemical space, achieving higher hit rates, and so forth. In this review, we focus on the most recent developments of FBDD for improving drug discovery, illustrating the process and the importance of FBDD. In particular, the computational strategies applied in the process of FBDD and molecular-docking programs are highlighted elaborately. In most cases, docking is used for predicting the ligand-receptor interaction modes and hit identification by structurebased virtual screening. The successful cases of typical significance and the hits identified most recently are discussed.

  4. Computer-Aided Drug Design Applied to Marine Drug Discovery: Meridianins as Alzheimer's Disease Therapeutic Agents.

    Science.gov (United States)

    Llorach-Pares, Laura; Nonell-Canals, Alfons; Sanchez-Martinez, Melchor; Avila, Conxita

    2017-11-27

    Computer-aided drug discovery/design (CADD) techniques allow the identification of natural products that are capable of modulating protein functions in pathogenesis-related pathways, constituting one of the most promising lines followed in drug discovery. In this paper, we computationally evaluated and reported the inhibitory activity found in meridianins A-G, a group of marine indole alkaloids isolated from the marine tunicate Aplidium , against various protein kinases involved in Alzheimer's disease (AD), a neurodegenerative pathology characterized by the presence of neurofibrillary tangles (NFT). Balance splitting between tau kinase and phosphate activities caused tau hyperphosphorylation and, thereby, its aggregation and NTF formation. Inhibition of specific kinases involved in its phosphorylation pathway could be one of the key strategies to reverse tau hyperphosphorylation and would represent an approach to develop drugs to palliate AD symptoms. Meridianins bind to the adenosine triphosphate (ATP) binding site of certain protein kinases, acting as ATP competitive inhibitors. These compounds show very promising scaffolds to design new drugs against AD, which could act over tau protein kinases Glycogen synthetase kinase-3 Beta (GSK3β) and Casein kinase 1 delta (CK1δ, CK1D or KC1D), and dual specificity kinases as dual specificity tyrosine phosphorylation regulated kinase 1 (DYRK1A) and cdc2-like kinases (CLK1). This work is aimed to highlight the role of CADD techniques in marine drug discovery and to provide precise information regarding the binding mode and strength of meridianins against several protein kinases that could help in the future development of anti-AD drugs.

  5. Drug Partitioning in Micellar Media and Its Implications in Rational Drug Design: Insights with Streptomycin.

    Science.gov (United States)

    Judy, Eva; Pagariya, Darshna; Kishore, Nand

    2018-03-20

    Oral bioavailability of a drug molecule requires its effective delivery to the target site. In general, majority of synthetically developed molecular entities have high hydrophobic nature as well as low bioavailability, therefore the need for suitable delivery vehicles arises. Self-assembled structures such as micelles, niosomes, and liposomes have been used as effective delivery vehicles and studied extensively. However, the information available in literature is mostly qualitative in nature. We have quantitatively investigated the partitioning of antibiotic drug streptomycin into cationic, nonionic, and a mixture of cationic and nonionic surfactant micelles and its interaction with the transport protein serum albumin upon subsequent delivery. A combination of calorimetry and spectroscopy has been used to obtain the thermodynamic signatures associated with partitioning and interaction with the protein and the resulting conformational changes in the latter. The results have been correlated with other class of drugs of different nature to understand the role of molecular features in the partitioning process. These studies are oriented toward understanding the physical chemistry of partitioning of a variety of drug molecules into suitable delivery vehicles and hence establishing structure-property-energetics relationships. Such studies provide general guidelines toward a broader goal of rational drug design.

  6. Drugs, Alcohol & Pregnancy.

    Science.gov (United States)

    Dye, Christina

    Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

  7. A Novel Design for Drug-Drug Interaction Alerts Improves Prescribing Efficiency.

    Science.gov (United States)

    Russ, Alissa L; Chen, Siying; Melton, Brittany L; Johnson, Elizabette G; Spina, Jeffrey R; Weiner, Michael; Zillich, Alan J

    2015-09-01

    Drug-drug interactions (DDIs) are common in clinical care and pose serious risks for patients. Electronic health records display DDI alerts that can influence prescribers, but the interface design of DDI alerts has largely been unstudied. In this study, the objective was to apply human factors engineering principles to alert design. It was hypothesized that redesigned DDI alerts would significantly improve prescribers' efficiency and reduce prescribing errors. In a counterbalanced, crossover study with prescribers, two DDI alert designs were evaluated. Department of Veterans Affairs (VA) prescribers were video recorded as they completed fictitious patient scenarios, which included DDI alerts of varying severity. Efficiency was measured from time-stamped recordings. Prescribing errors were evaluated against predefined criteria. Efficiency and prescribing errors were analyzed with the Wilcoxon signed-rank test. Other usability data were collected on the adequacy of alert content, prescribers' use of the DDI monograph, and alert navigation. Twenty prescribers completed patient scenarios for both designs. Prescribers resolved redesigned alerts in about half the time (redesign: 52 seconds versus original design: 97 seconds; p<.001). Prescribing errors were not significantly different between the two designs. Usability results indicate that DDI alerts might be enhanced by facilitating easier access to laboratory data and dosing information and by allowing prescribers to cancel either interacting medication directly from the alert. Results also suggest that neither design provided adequate information for decision making via the primary interface. Applying human factors principles to DDI alerts improved overall efficiency. Aspects of DDI alert design that could be further enhanced prior to implementation were also identified.

  8. Grid Based Technologies for in silico Screening and Drug Design.

    Science.gov (United States)

    Potemkin, Vladimir; Grishina, Maria

    2018-03-08

    Various techniques for rational drug design are presented in the paper. The methods are based on a substitution of antipharmacophore atoms of the molecules of training dataset by new atoms and/or group of atoms increasing the atomic bioactivity increments obtained at a SAR study. Furthermore, a design methodology based on the genetic algorithm DesPot for discrete optimization and generation of new drug candidate structures is described. Additionally, wide spectra of SAR approaches (3D/4D QSAR interior and exterior-based methods - BiS, CiS, ConGO, CoMIn, high-quality docking method - ReDock) using MERA force field and/or AlteQ quantum chemical method for correct prognosis of bioactivity and bioactive probability is described. The design methods are implemented now at www.chemosophia.com web-site for online computational services. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Modern Prodrug Design for Targeted Oral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Arik Dahan

    2014-10-01

    Full Text Available The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options.

  10. 32 CFR 700.1138 - Responsibilities concerning marijuana, narcotics, and other controlled substances.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Responsibilities concerning marijuana, narcotics... concerning marijuana, narcotics, and other controlled substances. (a) All personnel shall endeavor to prevent and eliminate the unauthorized use of marijuana, narcotics and other controlled substances within the...

  11. 75 FR 52780 - Designation of Nine Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2010-08-27

    ... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Nine Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated nine additional counties as High Drug Trafficking Areas pursuant to...

  12. 75 FR 21368 - Designation of Five Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2010-04-23

    ... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Five Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated five additional counties as High Drug Trafficking Areas pursuant to...

  13. HIV protease drug resistance and its impact on inhibitor design.

    Science.gov (United States)

    Ala, P J; Rodgers, J D; Chang, C H

    1999-07-01

    The primary cause of resistance to the currently available HIV protease inhibitors is the accumulation of multiple mutations in the viral protease. So far more than 20 substitutions have been observed in the active site, dimer interface, surface loops and flaps of the homodimer. While many mutations reduce the protease's affinity for inhibitors, others appear to enhance its catalytic efficiency. This high degree of genetic flexibility has made the protease an elusive drug target. The design of the next generation of HIV protease inhibitors will be discussed in light of the current structural information.

  14. Translations on Narcotics and Dangerous Drugs No. 294

    Science.gov (United States)

    1977-04-13

    surveillance over the activity of the smugglers. The investigations of Col Mahmud Fahmi and Lt Col ’Isam al-Tarsawi showed that the smuggler, Anwar Ibrahim...Mahmud Fahmi , It Col ’Isam al-Tarsawi, Lt Col Tariq Salim and It Col Muhammad Sha’rawi raided "the Jinn’s" house in ’Abidin and seized four large...Yesterday a car dealer and his associate were arraigned in court on charges of transporting 205 kg of hashish. The first accused was Reza

  15. Translations on Narcotics and Dangerous Drugs, Number 308

    Science.gov (United States)

    1977-07-01

    violation means death . Some of the prisoners have openly admitted that they have been subjected to coercion to employ their land for the cultivation of...salesmen for Lebanese smugglers of slow death . According to the same information, the Cypriot salesmen used to travel by small boats to Lebanese...Spanish Horseman ) slowly but surely going to the dogs because of crimes committed by heroin addicts. Every day, to his great annoyance, he

  16. Translations on Narcotics and Dangerous Drugs, Number 282.

    Science.gov (United States)

    1977-01-27

    Judicial Police agents Francisco Fernandez Marin and Jesus Godoy Garcia. The arrest of Humberto de los Angeles Gutierrez and dentist Mario Alberto ...National Defense. He replaces Lt Col Alberto Alonso Rodriguez who has been named deputy commander of the 52nd Infantry Battalion in Chihuahua City...to sell in that city. Gaico Veremo Jacama (grower) 42 years of age, rural worker, living in Chibabava. Joao Mahala (smoker) bachelor, 34 years old

  17. Translations on Narcotics and Dangerous Drugs, Number 313

    Science.gov (United States)

    1977-08-05

    Santa Luzia, more accurately, in the district of Centro de Joao Paulo. Five plantations were burned and 247 kilos of marihuana were seized in Aldeia...States. The prisoners are: Olegario Rodriguez Rodriguez, Jose Alberto Ruiz, Pablo Astorga Lozano, Oscar Angulo Picos, Rodolfo Chavez Picos, Miguel...federal agents had also arrested the brothers Mario and Jorge Alberto Sandoval with 250 kilos of marihuana in their possession which they had planned

  18. Translations on Narcotics and Dangerous Drugs No. 301.

    Science.gov (United States)

    1977-05-23

    One Escaped Escaped Crewman Treated for Burns, Leaves Country Briefs Marihuana Plantation Found in Cundinamarca 34 Marihuana ’Factory’ Raid 34...Azcapotzalco Battalion (Jorge Reyes E; EXCELSIOR, 13 Apr 77) 37 Traffickers, Aircraft, Marihuana Seized (Rafael Medina Cruz; EXCELSIOR, 12 Apr 77) 38...Former Federal Agent Denies Charges (EL DIARIO, 7 Apr 77) 39 Federal Agents Burn Marihuana Cache (EL DIARIO, 6 Apr 77) 41 Penitentiary

  19. Translations on Narcotics and Dangerous Drugs No. 304

    Science.gov (United States)

    1977-06-09

    50,000 and detained a man in Taman Sri Tebrau here yesterday. Johore Baru OCPD Superintendent A. Balaratnam told reporters that a police party led...by deputy OCPD [officer in charge of Police Department] (crime) David Madhavan laid ambush on a house follow- ing a tip-off from the public. They

  20. Translations on Narcotics and Dangerous Drugs No. 300.

    Science.gov (United States)

    1977-05-19

    Daraluman here yesterday evening. A six-man party led by the deputy OCPD [officer in charge of police department], acting ASP [assistant super...pans. Kulim OCPD Deputy Supt Raja Lope Bin Razman said police raided an uninhabited wooden house believed to have been used as a laboratory in Jalan

  1. Translations on Narcotics and Dangerous Drugs, Number 296.

    Science.gov (United States)

    1977-04-27

    Mazda Familia car with license plate H-2115 in front of the cooperative barber shop on Latha Street this morning. They seized 5 grams of heroin in 15...pesos on the black market. The police also illegally seized a 1963 Ford stake bed truck and a 1971 Ford truck belonging to the La Sierrita ejido...security service jeeps, disguised in the clothing worn by guards. Investigators claimed that they transferred from the jeep to a brown Ford LTD in the

  2. Translations on Narcotics and Dangerous Drugs, Number 314.

    Science.gov (United States)

    1977-08-15

    communists--drew up a list of "strategic export commodities" of the country, but at that time raw opium was but one of several items, next to coffee , tin...Commission stated, "estimates based on a variety of sources suggest tha^ eight to twenty million North Americans have at least tried cannabis . These...round. I suggest that the Government has shelved its cannabis legislation because it has thought it out and sounded it out, only to

  3. Translations on Narcotics and Dangerous Drugs No. 305

    Science.gov (United States)

    1977-06-17

    prosecutor; Augusto Caro Rojas, court reporter; Rodolfo Carvajal Florez, municipal employee; Orlando Carrascal Claro, inspector; Jesus Antonio Carrillo...Arturo Melo Diaz, judge; Rafael Mendez Buendia, judge; Tirso Mendez Herrera, professor; Rubiela Maria Mendez Mendez , judge; Luis Orlando Mendez ...Misael Roa Fonseca, jail guard; Jose Ignacio Roa Mendez , policeman; Jose Anibal Robles Alvarado, judge; Jorge Rocha Mahecha, govern- ment inspector

  4. Translations on Narcotics and Dangerous Drugs, Number 274

    Science.gov (United States)

    1976-12-02

    of heroin worth $250,000 at Sydney Airport on Saturday. Bernice Carol Devereaux, 23, and John Peter Griffin, 27, both of Tweed Heads, were charged...FRONTERIZO in Spanish 10 Oct 76 p 10-B [Text] The Federal Judicial Police, working under Commander Margarito Mendez Rico, has successfully... Mendez Rico reported that the ringleader of the marihuana traffickers had confessed that in the town of Parral, Chihuahua, he had "secured" another

  5. Translations on Narcotics and Dangerous Drugs, Number 309

    Science.gov (United States)

    1977-07-08

    whom he prefers to identify only as Luiz and Jorge, succeeded in purchasing a few grams of hashish and they all went to the Parque Lage in the Jardim...fact that hundreds of youths are turned down in secondary school and in the factories of the industrial zones of Ecatepec, Santa Clara, Xalostoc and

  6. Translations on Narcotics and Dangerous Drug No. 273

    Science.gov (United States)

    1976-11-26

    address Farahnaz Avenue, Mehrabad, age 25; Naser Aarakhani, butcher , age 2k; Mansur Sa’adatbakhsh; Da’ud Amini, age l8; Hoseyn Dastani...a police uniform was not to show off. Also arrested were: Hassan Nezam ’Ali, age 30, a poultry dealer living in Sarcheshmeh, with 3

  7. Translations on Narcotics and Dangerous Drugs, Number 312

    Science.gov (United States)

    1977-07-29

    Avia, must return to the United States today. The two lawyers, through peno- logist Pablo Salah Villamizar, who has jurisdiction over the pilots and...Arevalo, who drew up the opinion, and Dr Leonel Olivar Bonilla . Investigation to Be Broadened The Military Superior Court ordered the investigation...At first, the accused were being defended by attorney Pablo Acosta Reyes, who was replaced by Julio Nunez. The latter maintained the absolute

  8. Low energy nanoemulsification to design veterinary controlled drug delivery devices

    Directory of Open Access Journals (Sweden)

    Thierry F Vandamme

    2010-10-01

    Full Text Available Thierry F Vandamme, Nicolas Anton, University of Strasbourg, Faculty of Pharmacy, Illkirch Cedex, France; UMR CNRS 7199, Laboratoire de Conception et Application de Molécules Bioactives, équipe de Pharmacie Biogalénique, Illkirch Cedex, France,  This work is selected as Controlled Release Society Outstanding Veterinary Paper Award 2010Abstract: The unique properties of nanomaterials related to structural stability and quantum-scale reactive properties open up a world of possibilities that could be exploited to design and to target drug delivery or create truly microscale biological sensors for veterinary applications. We developed cost-saving and solvent-free nanoemulsions. Formulated with a low-energy method, these nanoemulsions can find application in the delivery of controlled amounts of drugs into the beverage of breeding animals (such as poultry, cattle, pigs or be used for the controlled release of injectable poorly water-soluble drugs.Keywords: nanoemulsion, nanomedicine, low-energy emulsification, veterinary, ketoprofen, sulfamethazine

  9. Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

    Science.gov (United States)

    Guedes, Karen Marinho Maciel; Borges, Rosivaldo Santos; Fontes-Júnior, Enéas Andrade; Silva, Andressa Santa Brigida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Pinto, Ana Carla Godinho; Silva, Mallone Lopes; Queiroz, Luana Melo Diogo; Vieira, José Luís Fernandes; Sousa, Pergentino José Cunha; Maia, Cristiane Socorro Ferraz

    2018-04-13

    Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

  10. Legal Aspects of Drug Abuse.

    Science.gov (United States)

    Sloat, Robert S.

    Discussed from a teacher's perspective are the legal and cultural ramifications of drug abuse. The importance of teachers' examining their own values concerning drug use is emphasized. Also reviewed are the history of drug use and of narcotics legislation. Recommendations concerning legislative reform are discussed. (CL)

  11. The impact of pharmacophore modeling in drug design.

    Science.gov (United States)

    Guner, Osman F

    2005-07-01

    With the reliable use of computer simulations in scientific research, it is possible to achieve significant increases in productivity as well as a reduction in research costs compared with experimental approaches. For example, computer-simulation can substantially enchance productivity by focusing the scientist to better, more informed choices, while also driving the 'fail-early' concept to result in a significant reduction in cost. Pharmacophore modeling is a reliable computer-aided design tool used in the discovery of new classes of compounds for a given therapeutic category. This commentary will briefly review the benefits and applications of this technology in drug discovery and design, and will also highlight its historical evolution. The two most commonly used approaches for pharmacophore model development will be discussed, and several examples of how this technology was successfully applied to identify new potent leads will be provided. The article concludes with a brief outline of the controversial issue of patentability of pharmacophore models.

  12. Frequency of Pathological Changes in Lungs of Bodies with Positive Postmortem Toxicology Results for Narcotics and Psychotropic Substances

    Directory of Open Access Journals (Sweden)

    Babak Mostafazadeh

    2017-01-01

    Full Text Available Background: The pattern of drug abuse in Iran has dramatically changed in recent years, turning from the traditional opioids [opium, opium dross, and refined opium dross (Shireh] into drugs with newer forms. The present study is aimed at investigating the frequency of pathological changes in the lungs of bodies with positive postmortem toxicology results for narcotics and psychotropic substances autopsied in the forensic dissection hall of Tehran, Iran [the Iranian Legal Medicine Organization (LMO]. Methods: The present study is a cross-sectional descriptive study. The sample consisted of 153 bodies, which had been referred to the LMO with positive results in postmortem toxicology for narcotics and psychotropic substances. Results: We found that narcotic drugs and psychotropic substances were used more in men than women. Moreover, the average age of death due to drug use was 36 years old. In addition, methamphetamine was the mostly-used type of substances, and smoking was the most widely used method to use the drugs. Besides, the dominant consistency and color of the lungs of half of the bodies investigated were elastic brown-gray. Moreover, the most common pathologic changes observed in the lungs of the bodies investigated were congestion and edema. Conclusion: Given the prevalence of pathological changes in the lungs of the examined bodies and congestion, edema, and pulmonary hemorrhage, the results of the present study can be particularly effective in determining the drug use and the resultant death in the absence of any previous records and/or a negative result of toxicology.

  13. Evaluation of Sociodemographic Determinants in Narcotic Users Referring to Center for Methadone Maintenance Therapy of Yazd, Iran

    Directory of Open Access Journals (Sweden)

    M.H. Lotfi

    2012-07-01

    Full Text Available Introduction: Addiction is a habit or behavior that is often hard to quit. It is estimated that 190 million persons are substance users around the world. Substance abuse creates tolerance after a while. Shortly after taking the drug, a person will not enjoy as the beginning of its use; that is why the amount of substance used is gradually increased. The purpose of this study was to find the reasons of tendency to narcotics among addicted individuals referred to methadone maintenance therapy (MMT center in Yazd. Materials & Methods: This study was a descriptive-analytic study on 100 addicts referred to methadone maintenance treatment center (MMT in Yazd. Data was collected by a pre-designed questionnaire with acceptable validity and reliability. Data was analyzed using SPSS statistical software and employing descriptive statistics such as percentage, ratio, mean, standard deviation and statistical tests such as t-test and chi- square was performed. Results: 41.9 % of addicts were unemployed, 4.77% married and 5.64% had elementary education. The most common method of substance consumption was inhalation (2.40%. Heroin was the most frequent type of substance used (1/51% The relationship between marital status and type of substance used, and age of onset of drug use was significant. The frequency of substance consumption was significantly different regarding the history of drug use in father, brother and spouses of patients in both sexes. Conclusion: Results of the current study showed that subjects at an early age (adolescence and early adulthood, individuals with low educational status, those with unstable jobs and low income, presence of addicted individuals among first-degree relatives can be the causes leading to addiction in the community.

  14. Biomembrane models and drug-biomembrane interaction studies: Involvement in drug design and development

    Directory of Open Access Journals (Sweden)

    R Pignatello

    2011-01-01

    Full Text Available Contact with many different biological membranes goes along the destiny of a drug after its systemic administration. From the circulating macrophage cells to the vessel endothelium, to more complex absorption barriers, the interaction of a biomolecule with these membranes largely affects its rate and time of biodistribution in the body and at the target sites. Therefore, investigating the phenomena occurring on the cell membranes, as well as their different interaction with drugs in the physiological or pathological conditions, is important to exploit the molecular basis of many diseases and to identify new potential therapeutic strategies. Of course, the complexity of the structure and functions of biological and cell membranes, has pushed researchers toward the proposition and validation of simpler two- and three-dimensional membrane models, whose utility and drawbacks will be discussed. This review also describes the analytical methods used to look at the interactions among bioactive compounds with biological membrane models, with a particular accent on the calorimetric techniques. These studies can be considered as a powerful tool for medicinal chemistry and pharmaceutical technology, in the steps of designing new drugs and optimizing the activity and safety profile of compounds already used in the therapy.

  15. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  16. The narcotic clinic in New Orleans, 1919-21.

    Science.gov (United States)

    Tallaksen, Amund

    2017-09-01

    This paper traces the history of the narcotic clinic in New Orleans, Louisiana, comparing its merits to a similar clinic in Shreveport. How do the clinics compare, and why did the Shreveport clinic operate for longer than its New Orleans counterpart? Qualitative analysis of contemporary medical journals and newspapers, as well as archival materials from the Narcotic Division. In addition, the records of Louisiana Governor John M. Parker, the papers of Dr Willis P. Butler in Shreveport, as well as the records of the Orleans Parish Medical Society have been utilized. The narcotic clinic in Shreveport benefited from strong local support, while the New Orleans clinic faced a more vocal opposition. In addition, the Shreveport clinic offered a broad array of services and was a pillar of the community; the New Orleans clinic was newly established and offered fewer services. It was especially the influx of out-of-state addicts that angered many New Orleanians, many of whom witnessed the addicts lined up in the French Quarter. The effectiveness of the narcotic clinics in Louisiana (1919-23) was influenced by local opinion. The New Orleans clinic faced a tougher political climate than its counterpart in Shreveport, and therefore proved less resilient in the face of federal opposition. © 2017 Society for the Study of Addiction.

  17. 30 CFR 57.20001 - Intoxicating beverages and narcotics.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Intoxicating beverages and narcotics. 57.20001 Section 57.20001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES...

  18. 30 CFR 56.20001 - Intoxicating beverages and narcotics.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Intoxicating beverages and narcotics. 56.20001 Section 56.20001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Miscellaneous...

  19. [Evaluation of color perception in individuals addicted to narcotic substances in the Farnsworth-Munsell 100-Hue test].

    Science.gov (United States)

    Nadolska, Krystyna; Goś, Roman

    2016-12-22

    The aim of the study was to assess color perception in the Farnsworth-Munsell 100-Hue test in individuals addicted to narcotic substances, and to analyze the acquired color vision disorders, depending on the duration of addiction and abstinence. Ninety-five persons were qualified for the study. All the subjects were divided into 3 groups. Group I (drug addicts) comprised 45 individuals addicted to narcotic substances and nicotine. Group II (smokers) consisted of 30 individuals addicted only to nicotine, and group III (abstinents) included 20 individuals free of addictions. In all the study groups anamnesis, survey, standard ophthalmological examination and the Farnsworth-Munsell 100-Hue test were performed. In the Farnsworth-Munsell 100-Hue test the mean values of total error score (TES) for the purposes of the analysis, expressed in the values of square root (√TES), proved to be significantly higher in group I than in the two other groups (p colors. The Farnsworth-Munsell 100-Hue test proved useful in the detection and assessment of acquired dyschromatopsy induced by narcotic substances. The observed disorders appeared to be dependent on the duration of addiction and abstinence. Med Pr 2016;67(6):777-785. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  20. The role of water molecules in computational drug design.

    Science.gov (United States)

    de Beer, Stephanie B A; Vermeulen, Nico P E; Oostenbrink, Chris

    2010-01-01

    Although water molecules are small and only consist of two different atom types, they play various roles in cellular systems. This review discusses their influence on the binding process between biomacromolecular targets and small molecule ligands and how this influence can be modeled in computational drug design approaches. Both the structure and the thermodynamics of active site waters will be discussed as these influence the binding process significantly. Structurally conserved waters cannot always be determined experimentally and if observed, it is not clear if they will be replaced upon ligand binding, even if sufficient space is available. Methods to predict the presence of water in protein-ligand complexes will be reviewed. Subsequently, we will discuss methods to include water in computational drug research. Either as an additional factor in automated docking experiments, or explicitly in detailed molecular dynamics simulations, the effect of water on the quality of the simulations is significant, but not easily predicted. The most detailed calculations involve estimates of the free energy contribution of water molecules to protein-ligand complexes. These calculations are computationally demanding, but give insight in the versatility and importance of water in ligand binding.

  1. Biomedical data integration in computational drug design and bioinformatics.

    Science.gov (United States)

    Seoane, Jose A; Aguiar-Pulido, Vanessa; Munteanu, Cristian R; Rivero, Daniel; Rabunal, Juan R; Dorado, Julian; Pazos, Alejandro

    2013-03-01

    In recent years, in the post genomic era, more and more data is being generated by biological high throughput technologies, such as proteomics and transcriptomics. This omics data can be very useful, but the real challenge is to analyze all this data, as a whole, after integrating it. Biomedical data integration enables making queries to different, heterogeneous and distributed biomedical data sources. Data integration solutions can be very useful not only in the context of drug design, but also in biomedical information retrieval, clinical diagnosis, system biology, etc. In this review, we analyze the most common approaches to biomedical data integration, such as federated databases, data warehousing, multi-agent systems and semantic technology, as well as the solutions developed using these approaches in the past few years.

  2. EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON.

    Science.gov (United States)

    Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam

    2015-09-01

    Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.

  3. Afghanistan: Narcotics and U.S. Policy

    Science.gov (United States)

    2008-01-24

    markets, and to restore wheat and other cereal crop production levels. Work began on phase one projects in early 2005 and continued through 2006...Barnett, “UK in Secret Biological War on Drugs,” Observer (London), September 17, 2000; Juanita Darling, “ Fungi May Be the Newest Recruits in War on Drugs

  4. Early predictors of narcotics-dependent patients in the emergency department

    Directory of Open Access Journals (Sweden)

    Wei-Che Lee

    2013-06-01

    Full Text Available It is not unusual that narcotics-dependent patients fulfill their medical requirements in the emergency department (ED. The behavior of these patients varies, and their manifestations and predictors are still not fully studied. We performed this retrospective study by prospectively collecting data on patients with suspected drug dependence who were undiagnosed at first and then treated for some kind of reported pain at the ED. Patients who were confirmed to have narcotics dependence were compared with control patients in a ratio of 1:3 matching for age, gender, disease, and clinical diagnoses. From January 2006 to October 2009, 26 of 223 patients treated for pain were found to be drug dependent (12 males and 14 females. The average dose of narcotics used was higher than the control group [3.23 ± 1.14 vs. 1.12 ± 0.36, p < 0.001, confidence interval (CI: 1.648–2.583]. Numbers of patients making unscheduled returns to the ED within 24 hours were significant [24/26 vs. 8/78, p ≤ 0.001, odds ratio (OR 105.00, 95% CI 20.834–529.175]. In addition, patients showing aggressive attitudes were significant (17/26 vs. 2/78, p < 0.001, OR 71.78, 95% CI 14.206–362.663. In the case group, six of them told the physician that they were allergic to medicines other than the particular one they wanted, and three of the six presented injuries that were reported to be in the same (or repeated place for unscheduled returns, which were not found in the control group. In this study, some behaviors were commonly observed in the at-risk group. These patients were prone to manifest some types of symptoms and behaviors, such as uncontrolled pain with three doses of analgesics, aggressive attitude, returning to the ED within 24 hours with the complaint of the same severe pain, repeating the same injury, claiming allergy to other analgesics, and asking for certain analgesics. All these behaviors should alert the physician to suspect a drug-seeking problem.

  5. Integrated Teaching of Structure-Based Drug Design and Biopharmaceutics: A Computer-Based Approach

    Science.gov (United States)

    Sutch, Brian T.; Romero, Rebecca M.; Neamati, Nouri; Haworth, Ian S.

    2012-01-01

    Rational drug design requires expertise in structural biology, medicinal chemistry, physiology, and related fields. In teaching structure-based drug design, it is important to develop an understanding of the need for early recognition of molecules with "drug-like" properties as a key component. That is, it is not merely sufficient to teach…

  6. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  7. Advanced drug delivery systems: Nanotechnology of health design A review

    Directory of Open Access Journals (Sweden)

    Javad Safari

    2014-04-01

    Full Text Available Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.

  8. Virtual fragment preparation for computational fragment-based drug design.

    Science.gov (United States)

    Ludington, Jennifer L

    2015-01-01

    Fragment-based drug design (FBDD) has become an important component of the drug discovery process. The use of fragments can accelerate both the search for a hit molecule and the development of that hit into a lead molecule for clinical testing. In addition to experimental methodologies for FBDD such as NMR and X-ray Crystallography screens, computational techniques are playing an increasingly important role. The success of the computational simulations is due in large part to how the database of virtual fragments is prepared. In order to prepare the fragments appropriately it is necessary to understand how FBDD differs from other approaches and the issues inherent in building up molecules from smaller fragment pieces. The ultimate goal of these calculations is to link two or more simulated fragments into a molecule that has an experimental binding affinity consistent with the additive predicted binding affinities of the virtual fragments. Computationally predicting binding affinities is a complex process, with many opportunities for introducing error. Therefore, care should be taken with the fragment preparation procedure to avoid introducing additional inaccuracies.This chapter is focused on the preparation process used to create a virtual fragment database. Several key issues of fragment preparation which affect the accuracy of binding affinity predictions are discussed. The first issue is the selection of the two-dimensional atomic structure of the virtual fragment. Although the particular usage of the fragment can affect this choice (i.e., whether the fragment will be used for calibration, binding site characterization, hit identification, or lead optimization), general factors such as synthetic accessibility, size, and flexibility are major considerations in selecting the 2D structure. Other aspects of preparing the virtual fragments for simulation are the generation of three-dimensional conformations and the assignment of the associated atomic point charges.

  9. Design and Evaluation of Chitosan-Based Novel pHSensitive Drug ...

    African Journals Online (AJOL)

    Design and Evaluation of Chitosan-Based Novel pHSensitive Drug Carrier for Sustained ... Scanning electron microscopy(SEM),Raman spectroscopy for particle size analysis. Swelling ratio, Effect of drug loading on encapsulation efficiency

  10. Reforming private drug coverage in Canada: inefficient drug benefit design and the barriers to change in unionized settings.

    Science.gov (United States)

    O'Brady, Sean; Gagnon, Marc-André; Cassels, Alan

    2015-02-01

    Prescription drugs are the highest single cost component for employees' benefits packages in Canada. While industry literature considers cost-containment for prescription drug costs to be a priority for insurers and employers, the implementation of cost-containment measures for private drug plans in Canada remains more of a myth than a reality. Through 18 semi-structured phone interviews conducted with experts from private sector companies, unions, insurers and plan advisors, this study explores the reasons behind this incapacity to implement cost-containment measures by examining how private sector employers negotiate drug benefit design in unionized settings. Respondents were asked questions on how employee benefits are negotiated; the relationships between the players who influence drug benefit design; the role of these players' strategies in influencing plan design; the broad system that underpins drug benefit design; and the potential for a universal pharmacare program in Canada. The study shows that there is consensus about the need to educate employees and employers, more collaboration and data-sharing between these two sets of players, and for external intervention from government to help transform established norms in terms of private drug plan design. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. The Effects of Psychotropic Drugs.

    Science.gov (United States)

    Bonnardeaux, Jef-Louis

    1984-01-01

    Presents information on psychotropic drugs for individuals who are not specialists in pharmacology. Discusses: alcohol and barbituates; dependence and withdrawal; central nervous system depressors (anaesthetics, narcotic analgesics, sedatives and hypnotic drugs, tranquilizers), central nervous stimulants (amphetamines, cocaine, tobacco, caffeine),…

  12. Effectiveness of narcotics anonymous training programs in personality characters in substance abuse patients

    Directory of Open Access Journals (Sweden)

    Namat Sotodeh Asl

    2013-03-01

    Full Text Available Introduction: Substance abuse is one of the most common disorders that exert a high impact on the life of patients and their families. There are many treatment methods for Addiction. The purpose of the present study was to determine the effects of narcotics anonymous (NA program on personality characters in substance abuse patients.Materials and Methods: This quasi experimental design was performed on 100 patients with substance abuse disorders that they had been randomly selected from those patients who were referred to psychiatric clinics and counseling centers in Esfehan in 2008. Then, the subjects were equally divided into two groups; experimental and control. All the patients carried out Eysenk test prior to any intervention and also a demographic questionnaire were filled out by all the subjects. Then, Eysenk test was performed on all the patients following the intervention. Changing in personality character in the experimental group (before and after the intervention was compared with those of the control group. Results: The findings showed that narcotic program has significant effects on personality characters of experimental group to substance abuse in post test, but these effects are not significant in control group.Conclusion: According to the findings of this work, we suggest the effectiveness of NA program in changing personality characters of the patients with substance abuse

  13. The Ultimum Remedium Principle In The Context Of Criminal Punishment Against Children As An Actor Of Narcotics Crime

    Directory of Open Access Journals (Sweden)

    Syachdin

    2015-08-01

    Full Text Available Abstract Drug abuse has grown over the days with significant development. Narcotics crime actually not only brings individual actors but tends to be a criminal offense syndicate or covert organization over the worlds. In this case the syndicate allegedly not only brings perpetrators of adults but feared the actors who are categorized as a child in accordance with the applicable laws. On the other side children occupy a special place in the law. Basic philosophy of the treatment of juvenile delinquents is for the best interests of the child but the fact that peoples behavior lately is very alarming how society is so easy to judge people suspected as perpetrators of criminal acts. The objective of this research is to understand the essence of the ultimum remedium principle as the basis for criminal punishment in the Indonesian criminal system in order to understand how the crisis is influencing drug phenomenon and drugs users lives and the extent of their impact on the settlement of narcotics crime against children as an offender. The outcomes of the research indicate that the Law No. 11 of 2012 regarding the Criminal Justice System for Juvenile Delinquency Rules of the Supreme Court of the Republic of Indonesia No. 4 of 2014 on Guidelines for Diversion and Law No. 35 of 2009 regarding Narcotics Crime have been given the freedom and legitimacy to the judge to apply the principle of ultimum remedium in handling cases of children in conflict with the law. As it turns out in practice however the ultimum remedium principle is rarely applied and tends to be overlooked in the process of juvenile justice.

  14. Taking aim at a moving target: designing drugs to inhibit drug-resistant HIV-1 reverse transcriptases.

    Science.gov (United States)

    Sarafianos, Stefan G; Das, Kalyan; Hughes, Stephen H; Arnold, Eddy

    2004-12-01

    HIV undergoes rapid genetic variation; this variation is caused primarily by the enormous number of viruses produced daily in an infected individual. Because of this variation, HIV presents a moving target for drug and vaccine development. The variation within individuals has led to the generation of diverse HIV-1 subtypes, which further complicates the development of effective drugs and vaccines. In general, it is more difficult to hit a moving target than a stationary target. Two broad strategies for hitting a moving target (in this case, HIV replication) are to understand the movement and to aim at the portions that move the least. In the case of anti-HIV drug development, the first option can be addressed by understanding the mechanism(s) of drug resistance and developing drugs that effectively inhibit mutant viruses. The second can be addressed by designing drugs that interact with portions of the viral machinery that are evolutionarily conserved, such as enzyme active sites.

  15. Heuristic lipophilicity potential for computer-aided rational drug design

    Science.gov (United States)

    Du, Qishi; Arteca, Gustavo A.; Mezey, Paul G.

    1997-09-01

    In this contribution we suggest a heuristic molecular lipophilicitypotential (HMLP), which is a structure-based technique requiring noempirical indices of atomic lipophilicity. The input data used in thisapproach are molecular geometries and molecular surfaces. The HMLP is amodified electrostatic potential, combined with the averaged influences fromthe molecular environment. Quantum mechanics is used to calculate theelectron density function ρ(r) and the electrostatic potential V(r), andfrom this information a lipophilicity potential L(r) is generated. The HMLPis a unified lipophilicity and hydrophilicity potential. The interactions ofdipole and multipole moments, hydrogen bonds, and charged atoms in amolecule are included in the hydrophilic interactions in this model. TheHMLP is used to study hydrogen bonds and water-octanol partitioncoefficients in several examples. The calculated results show that the HMLPgives qualitatively and quantitatively correct, as well as chemicallyreasonable, results in cases where comparisons are available. Thesecomparisons indicate that the HMLP has advantages over the empiricallipophilicity potential in many aspects. The HMLP is a three-dimensional andeasily visualizable representation of molecular lipophilicity, suggested asa potential tool in computer-aided three-dimensional drug design.

  16. The ways and means of fragment-based drug design.

    Science.gov (United States)

    Doak, Bradley C; Norton, Raymond S; Scanlon, Martin J

    2016-11-01

    Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to develop high-affinity ligands against protein targets. One of the strengths of FBDD is the relative ease and low cost of the primary screen to identify fragments that bind. However, the fragments that emerge from primary screens often have low affinities, with K D values in the high μM to mM range, and a significant challenge for FBDD is to develop the initial fragments into more potent ligands. Successful fragment elaboration often requires co-structures of the fragments bound to their target proteins, as well as a range of biophysical and biochemical assays to track potency and efficacy. These challenges have led to the development of specific chemical strategies for the elaboration of weakly-binding fragments into more potent "hits" and lead compounds. In this article we review different approaches that have been employed to meet these challenges and describe some of the strategies that have resulted in several fragment-derived compounds entering clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Peptide-based proteasome inhibitors in anticancer drug design.

    Science.gov (United States)

    Micale, Nicola; Scarbaci, Kety; Troiano, Valeria; Ettari, Roberta; Grasso, Silvana; Zappalà, Maria

    2014-09-01

    The identification of the key role of the eukaryotic 26S proteasome in regulated intracellular proteolysis and its importance as a target in many pathological conditions wherein the proteasomal activity is defective (e.g., malignancies, autoimmune diseases, neurodegenerative diseases, etc.) prompted several research groups to the development of specific inhibitors of this multicatalytic complex with the aim of obtaining valid drug candidates. In regard to the anticancer therapy, the peptide boronate bortezomib (Velcade®) represents the first molecule approved by FDA for the treatment of multiple myeloma in 2003 and mantle cell lymphoma in 2006. Since then, a plethora of molecules targeting the proteasome have been identified as potential anticancer agents and a few of them reached clinical trials or are already in the market (i.e., carfilzomib; Kyprolis®). In most cases, the design of new proteasome inhibitors (PIs) takes into account a proven peptide or pseudopeptide motif as a base structure and places other chemical entities throughout the peptide skeleton in such a way to create an efficacious network of interactions within the catalytic sites. The purpose of this review is to provide an in-depth look at the current state of the research in the field of peptide-based PIs, specifically those ones that might find an application as anticancer agents. © 2014 Wiley Periodicals, Inc.

  18. Narcotic smuggling and radiography of the gastrointestinal tract

    International Nuclear Information System (INIS)

    Pamilo, M.; Suoranta, H.; Suramo, I.

    1986-01-01

    The gastrointestinal tract is being used to an increasing extent as a route for smuggling narcotics. Small, swallowed packages overwrapped with condoms or other materials are usually not detected by the customs authorities. Conventional abdominal radiography may indicate foreign bodies surrounded by a characteristic thin layer of gas and located in the gastrointestinal tract. Some short case histories, and the radiologic findings in four heroin 'body packers' are presented. (orig.)

  19. Paediatric Drug Development and Formulation Design-a European Perspective

    NARCIS (Netherlands)

    Nales, D.A.; Kozarewicz, Piotr; Aylward, Brian; de Vries, Rutger; Egberts, Toine C G; Rademaker, Carin M A; Schobben, Alfred F A M

    The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed

  20. Design and Development of a Proniosomal Transdermal Drug ...

    African Journals Online (AJOL)

    Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

  1. Using Free Computational Resources to Illustrate the Drug Design Process in an Undergraduate Medicinal Chemistry Course

    Science.gov (United States)

    Rodrigues, Ricardo P.; Andrade, Saulo F.; Mantoani, Susimaire P.; Eifler-Lima, Vera L.; Silva, Vinicius B.; Kawano, Daniel F.

    2015-01-01

    Advances in, and dissemination of, computer technologies in the field of drug research now enable the use of molecular modeling tools to teach important concepts of drug design to chemistry and pharmacy students. A series of computer laboratories is described to introduce undergraduate students to commonly adopted "in silico" drug design…

  2. 77 FR 74195 - Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for...

    Science.gov (United States)

    2012-12-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-1161] Draft Guidance for Industry and Food and Drug Administration Staff; Design Considerations for Devices Intended for Home Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

  3. Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design

    Science.gov (United States)

    Ishikawa, Toshihisa; Tamura, Ai; Saito, Hikaru; Wakabayashi, Kanako; Nakagawa, Hiroshi

    2005-10-01

    In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development. Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines. Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least 30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may greatly facilitate drug development and allow the prediction of drug-drug interactions. We recently developed methods for high-speed functional screening and quantitative structure-activity relationship analysis to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues that can circumvent AGCG2-associated multidrug resistance of cancer.

  4. 21 CFR 516.36 - Insufficient quantities of MUMS-designated drugs.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.36 Insufficient quantities of... the 7-year period of exclusive marketing rights. (b) If, within the time that FDA specifies, the...

  5. Hypothesis driven drug design: improving quality and effectiveness of the design-make-test-analyse cycle.

    Science.gov (United States)

    Plowright, Alleyn T; Johnstone, Craig; Kihlberg, Jan; Pettersson, Jonas; Robb, Graeme; Thompson, Richard A

    2012-01-01

    In drug discovery, the central process of constructing and testing hypotheses, carefully conducting experiments and analysing the associated data for new findings and information is known as the design-make-test-analyse cycle. Each step relies heavily on the inputs and outputs of the other three components. In this article we report our efforts to improve and integrate all parts to enable smooth and rapid flow of high quality ideas. Key improvements include enhancing multi-disciplinary input into 'Design', increasing the use of knowledge and reducing cycle times in 'Make', providing parallel sets of relevant data within ten working days in 'Test' and maximising the learning in 'Analyse'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Identification of novel Mycobacterium tuberculosis dihydrofolate reductase inhibitors through rational drug design

    Directory of Open Access Journals (Sweden)

    Mymoona Akhter

    2016-01-01

    Conclusion: Structure based drug design can be used as an effective tool for the design of new cheiocal entity. Number of novel agents have been identified as antitubercular agents whose mechanism of action needs to be ascertained.

  7. Drug design: structure- and ligand-based approaches

    National Research Council Canada - National Science Library

    Merz, Kenneth M; Ringe, Dagmar; Reynolds, Charles H

    2010-01-01

    ..., computational ADME-Tox, and drug discovery case studies. A variety of authors from academic and commercial institutions all over the world have contributed to this book, which is illustrated with more than 200 images...

  8. Membrane Transporters: Structure, Function and Targets for Drug Design

    Science.gov (United States)

    Ravna, Aina W.; Sager, Georg; Dahl, Svein G.; Sylte, Ingebrigt

    Current therapeutic drugs act on four main types of molecular targets: enzymes, receptors, ion channels and transporters, among which a major part (60-70%) are membrane proteins. This review discusses the molecular structures and potential impact of membrane transporter proteins on new drug discovery. The three-dimensional (3D) molecular structure of a protein contains information about the active site and possible ligand binding, and about evolutionary relationships within the protein family. Transporters have a recognition site for a particular substrate, which may be used as a target for drugs inhibiting the transporter or acting as a false substrate. Three groups of transporters have particular interest as drug targets: the major facilitator superfamily, which includes almost 4000 different proteins transporting sugars, polyols, drugs, neurotransmitters, metabolites, amino acids, peptides, organic and inorganic anions and many other substrates; the ATP-binding cassette superfamily, which plays an important role in multidrug resistance in cancer chemotherapy; and the neurotransmitter:sodium symporter family, which includes the molecular targets for some of the most widely used psychotropic drugs. Recent technical advances have increased the number of known 3D structures of membrane transporters, and demonstrated that they form a divergent group of proteins with large conformational flexibility which facilitates transport of the substrate.

  9. Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.

    Science.gov (United States)

    Nagai, Noriaki

    2016-01-01

    The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.

  10. Quantum mechanics implementation in drug-design workflows: does it really help? [Corrigendum

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2017-11-01

    Full Text Available Arodola OA, Soliman MES. Quantum mechanics implementation in drug-design workflows: does it really help? Drug Design, Development and Therapy. 2017;11:2551–2564.Figure 3 on page 2557 contains errors. The correct figure is shown.Read the original article

  11. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    Science.gov (United States)

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  12. Effects of narcotics on the endocrine system

    International Nuclear Information System (INIS)

    Zil, M.

    1990-01-01

    Endocrinological assessment of group of heroin addicts (n=91) was done and those who underwent full detoxification procedure (n=31) were also followed up after treatment. Pre and post detoxification evaluation included estimation of growth hormone (GH), follicle stimulating hormone (FSH), leuteinizing hormone (LH), thyroid stimulating hormone (TSH), prolactin (PRL), testosterone (TEST), estradiol (EST), cortisol (CORT), insulin (INS) and Free Thyroxine (FT4). Factors like duration of drug abuse, polydrug addiction, hepatic function status, age of abusers and dose including cumulative dose were also assessed but no significant bearing on the results was elicited. Difference between pre and post detoxification hormonal levels was highly significant in growth hormone, Testosterone, and prolactin values and less significant for FSH, ESTRADIOL, FT4 and TSH. But for a few exceptions, our results compared well with those reported in the literature and compare with reflect the widespread hormonal and endocrinological aberrations noted in heroin addicts. (author)

  13. Control authorities of internal affairs bodies in the sphere of drug trafficking

    Directory of Open Access Journals (Sweden)

    О. М. Шевчук

    2014-06-01

    Full Text Available The article deals with control authorities of internal Affairs bodies in the sphere of turnover of narcotic drugs, psychotropic substances and precursors. Established the concept of the legal status of the Management of the fight against illegal circulation of drugs of the Ministry of interior of Ukraine and describes its features. The classification of control authorities of internal Affairs bodies in the sphere of turnover of narcotic drugs, psychotropic substances and precursors and analyzed for their content.

  14. Specifics of Chemical Toxilogical Analyses in the Russian Federation for the Purpose of Identification of Narcotics in Biological Matters

    Energy Technology Data Exchange (ETDEWEB)

    Coates, Cameron W [ORNL; Eisele, Gerhard R [ORNL

    2011-01-01

    The Russian Federation (RF) is committed to implementing a comprehensive drug testing program under its Personnel Reliability Program (PRP) for military personnel involved in handling sensitive nuclear materials. This commitment leads to a number of mandatory requirements for the laboratory conducting the confirmation testing to ensure the legitimacy and integrity of the testing process. These requirements are established by the RF Duma to ensure that individuals conducting these tests have adequate training, certifications, and experience to conduct narcotic confirmation tests. This paper describes the facility requirements and personnel qualifications needed for conducting comprehensive drug abuse confirmation testing. Details regarding the personnel training and laboratory experience in the theory and practice of analytical forensic toxicology of drugs of abuse will be presented, as well as the facility requirements for the laboratory conducting such tests. Chain-of-custody, from sample receipt through completion of testing, reporting of results, and continuing until final disposition of specimens will be addressed.

  15. Risk-taking related to drug use: an application of the shift-to-risk design.

    Science.gov (United States)

    Deren, S; Des Jarlais, D C

    1977-01-01

    The utility of the shift-to-risk design for studying the influence of peer groups on drug taking was investigated. Two studies using this design with drug content were conducted, varying the level of information provided about a drug. Subjects were from two college classes consisting of 26 and 28 students. Results indicated that the specification of possible harmful drug effects which are somewhat minimal lead to a significantly greater willingness to recommend trying the drug. In addition, a tendency for a shift-to-caution was found. It was concluded that the shift-to-risk designwas useful for studying decision-making regarding drug use, and that both users and nonusers of drugs should be included in future research.

  16. Quantitative modeling of selective lysosomal targeting for drug design

    DEFF Research Database (Denmark)

    Trapp, Stefan; Rosania, G.; Horobin, R.W.

    2008-01-01

    log K ow. These findings were validated with experimental results and by a comparison to the properties of antimalarial drugs in clinical use. For ten active compounds, nine were predicted to accumulate to a greater extent in lysosomes than in other organelles, six of these were in the optimum range...... predicted by the model and three were close. Five of the antimalarial drugs were lipophilic weak dibasic compounds. The predicted optimum properties for a selective accumulation of weak bivalent bases in lysosomes are consistent with experimental values and are more accurate than any prior calculation...

  17. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

    Directory of Open Access Journals (Sweden)

    Lucianna Helene Santos

    2015-11-01

    Full Text Available Reverse transcriptase (RT is a multifunctional enzyme in the human immunodeficiency virus (HIV-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

  18. 14 CFR 65.12 - Offenses involving alcohol or drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Offenses involving alcohol or drugs. 65.12... alcohol or drugs. (a) A conviction for the violation of any Federal or state statute relating to the... narcotic drugs, marihuana, or depressant or stimulant drugs or substances is grounds for— (1) Denial of an...

  19. 14 CFR 63.12 - Offenses involving alcohol or drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Offenses involving alcohol or drugs. 63.12... alcohol or drugs. (a) A conviction for the violation of any Federal or state statute relating to the... narcotic drugs, marihuana, or depressant or stimulant drugs or substances is grounds for— (1) Denial of an...

  20. Drug Abuse. A Guide for Parents and Teachers.

    Science.gov (United States)

    St. Souver, F. Gerald; Plunkett, Thomas G.

    This booklet is concerned with providing information on drug abuse. A brief history of drug traffic and today's problem begin the pamphlet. The second part discusses the identification of drugs including opium, heroin, and marihuana. The next section is concerned with non-narcotic drug abuse, including Lysergic Acid Diethylamide (LSD) mascaline,…

  1. Beyond THC: the new generation of cannabinoid designer drugs

    Directory of Open Access Journals (Sweden)

    Liana eFattore

    2011-09-01

    Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC, the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naïve individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

  2. DRUGS – “WAY” OF LIFE

    Directory of Open Access Journals (Sweden)

    Anna Nowacka

    2010-12-01

    Full Text Available This article refers to the phenomenon of an increasing number of people abusing drugs in the 20th century. In addition to the natural types of narcotics there are many other semi-synthetic and fully synthetic substances made available to the market by chemical and pharmaceutical industries. The use of narcotics and psychoactive substances usually causes adverse and often irreversible health effects. In Department of Laboratory Diagnostics of the Institute of Occupational Medicine and Environmental Health in Sosnowiec tests for presence of drugs are among routinely conducted analyses. The presence of drugs has been revealed in 898 cases between the years 2004 and 2008. On top of the list of the most frequently detected narcotics were: amphetamine, cannabis, opiates, methamphetamine and cocaine. At the same time the most popular psychoactive substances are atropine, scopolamine and psilocybin. Additionally, the laboratory analyses indicated in many cases the presence of derivatives of benzodiazepines, trycyclic antidepressants and alcohol. Regional Centre of Acute Intoxication in Sosnowiec, Poland, hospitalized 78 patients due to overdose of drugs, narcotics or psychoactive substances as a result of experimenting with such substances. Half of the hospitalized cases patients have tried to commit suicide; one of the attempts has led to death. According to patients’ history their problems with reaching out for the use of psychoactive substances and narcotics were mainly caused by socio-psychological disorders.

  3. Computational drug designing of fungal pigments as potential aromatase inhibitors

    Directory of Open Access Journals (Sweden)

    Nighat Fatima

    2014-12-01

    Full Text Available The existing aromatase inhibitors produced unwelcome effects impose the discovery of novel drugs with privileged selectivity, a reduced amount of toxicity and humanizing potency. In this study, we illuminate the binding mode of polyketide azaphilanoid pigments monascin, ankaflavin, monascorubrin and monascorubramine isolated from Monascus fungus to the aromatase by molecular docking. The 3-dimensional structure of aromatase enzyme (PDB: 4KQ8 was obtained from the Protein Data Bank. PatchDock docking software was used to analyze structural complexes of the aromatase with monascus pigments. Comparatively, the AutoGrid model presented the most briskly constructive binding mode of monascin to aromatase. Docked energies in kcal/mol are: monascin;-13.2; monascorubramine:-12.8, monascorubrin:-12.3; ankaflavin: -10.5. These outcomes exposed these ligands could be potential drugs to treat hormone dependent breast cancer.

  4. Design of Drug Delivery Systems Containing Artemisinin and Its Derivatives

    Directory of Open Access Journals (Sweden)

    Blessing Atim Aderibigbe

    2017-02-01

    Full Text Available Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically by their poor bioavailability, short half-life in vivo, poor water solubility and long term usage results in toxicity. They are also expensive for the treatment of malaria when compared to other antimalarials. In order to enhance their therapeutic efficacy, they are incorporated onto different drug delivery systems, thus yielding improved biological outcomes. This review article is focused on the currently synthesized derivatives of artemisinin and different delivery systems used for the incorporation of artemisinin and its derivatives.

  5. Fragment-based drug discovery using rational design.

    Science.gov (United States)

    Jhoti, H

    2007-01-01

    Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

  6. [The role of biotechnology in pharmaceutical drug design].

    Science.gov (United States)

    Gaisser, Sibylle; Nusser, Michael

    2010-01-01

    Biotechnological methods have become an important tool in pharmaceutical drug research and development. Today approximately 15 % of drug revenues are derived from biopharmaceuticals. The most relevant indications are oncology, metabolic disorders and disorders of the musculoskeletal system. For the future it can be expected that the relevance of biopharmaceuticals will further increase. Currently, the share of substances in preclinical testing that rely on biotechnology is more than 25 % of all substances in preclinical testing. Products for the treatment of cancer, metabolic disorders and infectious diseases are most important. New therapeutic approaches such as RNA interference only play a minor role in current commercial drug research and development with 1.5 % of all biological preclinical substances. Investments in sustainable high technology such as biotechnology are of vital importance for a highly developed country like Germany because of its lack of raw materials. Biotechnology helps the pharmaceutical industry to develop new products, new processes, methods and services and to improve existing ones. Thus, international competitiveness can be strengthened, new jobs can be created and existing jobs preserved.

  7. Design of a tripartite network for the prediction of drug targets

    Science.gov (United States)

    Kunimoto, Ryo; Bajorath, Jürgen

    2018-02-01

    Drug-target networks have aided in many target prediction studies aiming at drug repurposing or the analysis of side effects. Conventional drug-target networks are bipartite. They contain two different types of nodes representing drugs and targets, respectively, and edges indicating pairwise drug-target interactions. In this work, we introduce a tripartite network consisting of drugs, other bioactive compounds, and targets from different sources. On the basis of analog relationships captured in the network and so-called neighbor targets of drugs, new drug targets can be inferred. The tripartite network was found to have a stable structure and simulated network growth was accompanied by a steady increase in assortativity, reflecting increasing correlation between degrees of connected nodes leading to even network connectivity. Local drug environments in the tripartite network typically contained neighbor targets and revealed interesting drug-compound-target relationships for further analysis. Candidate targets were prioritized. The tripartite network design extends standard drug-target networks and provides additional opportunities for drug target prediction.

  8. Application of in situ polymerization for design and development of oral drug delivery systems.

    Science.gov (United States)

    Ngwuluka, Ndidi

    2010-12-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  9. Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems

    OpenAIRE

    Ngwuluka, Ndidi

    2010-01-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  10. TRPV1: A Target for Rational Drug Design

    Directory of Open Access Journals (Sweden)

    Vincenzo Carnevale

    2016-08-01

    Full Text Available Transient Receptor Potential Vanilloid 1 (TRPV1 is a non-selective, Ca2+ permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX. Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures.

  11. Towards appropriate design solutions for drug-resistant TB facilities in SA

    CSIR Research Space (South Africa)

    Parsons, SA

    2010-07-01

    Full Text Available South Africa has a high and increasing burden of both drugs-susceptible and drug-resistant tuberculosis. This disease has been declared an emergency in Africa. South Africa has committed itself to addressing this national crises by designing...

  12. In silico ADME in drug design – enhancing the impact

    Directory of Open Access Journals (Sweden)

    Susanne Winiwarter

    2018-03-01

    Full Text Available Each year the pharmaceutical industry makes thousands of compounds, many of which do not meet the desired efficacy or pharmacokinetic properties, describing the absorption, distribution, metabolism and excretion (ADME behavior. Parameters such as lipophilicity, solubility and metabolic stability can be measured in high throughput in vitro assays. However, a compound needs to be synthesized in order to be tested. In silico models for these endpoints exist, although with varying quality. Such models can be used before synthesis and, together with a potency estimation, influence the decision to make a compound. In practice, it appears that often only one or two predicted properties are considered prior to synthesis, usually including a prediction of lipophilicity. While it is important to use all information when deciding which compound to make, it is somewhat challenging to combine multiple predictions unambiguously. This work investigates the possibility of combining in silico ADME predictions to define the minimum required potency for a specified human dose with sufficient confidence. Using a set of drug discovery compounds,in silico predictions were utilized to compare the relative ranking based on minimum potency calculation with the outcomes from the selection of lead compounds. The approach was also tested on a set of marketed drugs and the influence of the input parameters investigated.

  13. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

    Science.gov (United States)

    Bian, Yuemin; Xie, Xiang-Qun Sean

    2018-04-09

    Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

  14. Marijuana-based Drugs: Innovative Therapeutics or Designer Drugs of Abuse?

    OpenAIRE

    Seely, Kathryn A.; Prather, Paul L.; James, Laura P.; Moran, Jeffery H.

    2011-01-01

    Marijuana has been used recreationally and medicinally for centuries. The principle psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC), activates CB1 cannabinoid receptors (CB1Rs). CB1R agonists and antagonists could potentially treat a wide variety of diseases; unfortunately, therapeutic doses produce unacceptable psychiatric effects. “K2” or “Spice” (K2/Spice), an emerging drug of abuse, exhibits psychotropic actions via CB1R activation. Because of structural dissimilarity to Δ9-THC, ...

  15. The experience of childbrith in first-time mothers who received narcotic analgesics during the first stage of labour.

    Science.gov (United States)

    Jantjes, L; Strümpher, J; Kotzé, W J

    2007-06-01

    This research has focused on the birthing experience of first-time mothers who received the narcotic analgesic combination of Pethidine and Hydroxyzine during the first stage of labour. A qualitative research methodology was used to collect data. Unstructured interviews were held with first-time mothers to obtain accounts of their experience of childbirth. These narrations were audio-taped while the participants were still being cared for in the postnatal ward of the hospital where delivery took place. Nine interviews were conducted with first-time mothers who gave birth normally vaginally after a normal pregnancy and who received a narcotic analgesic in the first stage of labour. The transcribed interviews were analyzed using Tesch's method of descriptive analysis (in Creswell, 1994:115). Four themes with sub-themes emerged from the analysis. The participants reported on the physical experience of labour and described experiencing a lot of pain for which analgesics were given. They also described how these drugs dulled the pain but made them sleepy and unable to cooperate with the midwives. They described their emotional experiences, which included joy and happiness as well as anxiety, anger and despondence. They also reported that they were not sufficiently informed about labour and child-birth. In the last theme they described the methods they used to help them cope with labour including distracting techniques, leaning on a supportive person or praying. Guidelines to help midwives overcome these problems were developed.

  16. Comparison of results for morphine urinalyses by radioimmunoassay and thin-layer chromatography in a narcotic clinic setting.

    Science.gov (United States)

    Kokoski, R J; Jain, M

    1975-03-01

    Radioimmunoassay (RIA) and thin-layer chromatography (TLC) were compared for morphine detection in an actual narcotic clinic setting. A choice of urines from all those screened by TLC allowed a critical comparison as to actual use or non-use of narcotic drugs, rather than a sampling at random in which the question of possible false positives or negatives cannot be conclusively answered. Although RIA is more sensitive than TLC, its advantage is apparent only in those cases where urine specimens are difficult to obtain frequently regularly or where the use of morphine is suspected by the positive identification of quinine in urine that was morphine-negative by TLC. In a selected group of negative and positive specimens chosen without conscious bias, the two methods gave consistently similar results, indicating that the modified TLC method provided a few or no false positives or negatives if the negatives were from those cases that were not positive anytime up to 3-4 days before urine collection. We conclude that RIA can be of significant value as a supplement to a TLC screening program, without sacrificing the many advantages that TLC has to offer.

  17. The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines.

    Science.gov (United States)

    Poirier, A F; Murphy, W R

    2016-12-01

    The US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA, 2012) introduced the Breakthrough Therapy Designation (BTD), a new tool to expedite development of medicines to treat serious or life-threatening diseases. The majority of BTDs have gone to oncology drugs, and a recent publication by Shea et al. 1 reviewed the impact of BTD on oncology drug development. This article reviews the impact of BTD on development strategies and timelines for nononcology drugs. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  18. Applications of Monte Carlo technique in the detection of explosives, narcotics and fissile material using neutron sources

    International Nuclear Information System (INIS)

    Sinha, Amar; Kashyap, Yogesh; Roy, Tushar; Agrawal, Ashish; Sarkar, P.S.; Shukla, Mayank

    2009-01-01

    The problem of illicit trafficking of explosives, narcotics or fissile materials represents a real challenge to civil security. Neutron based detection systems are being actively explored worldwide as a confirmatory tool for applications in the detection of explosives either hidden inside a vehicle or a cargo container or buried inside soil. The development of a system and its experimental testing is a tedious process and to develop such a system each experimental condition needs to be theoretically simulated. Monte Carlo based methods are used to find an optimized design for such detection system. In order to design such systems, it is necessary to optimize source and detector system for each specific application. The present paper deals with such optimization studies using Monte Carlo technique for tagged neutron based system for explosives and narcotics detection hidden in a cargo and landmine detection using backscatter neutrons. We will also discuss some simulation studies on detection of fissile material and photo-neutron source design for applications on cargo scanning. (author)

  19. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

    Science.gov (United States)

    Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

    2018-02-01

    For a drug, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  20. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

    Directory of Open Access Journals (Sweden)

    Hongbin Yang

    2018-02-01

    Full Text Available During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  1. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts.

    Science.gov (United States)

    Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

    2018-01-01

    During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

  2. Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR

    DEFF Research Database (Denmark)

    Narayanan, Dilip; Gani, Osman ABSM; Gruber, Franz XE

    2017-01-01

    encoded into molecular mechanics force fields. Cheminformatics analyses of binding data show EGFR to be dissimilar to ALK and MET, but its structure shows how it may be co-targeted with the addition of a covalent trap. This suggests a strategy for the design of a focussed chemical library based on a pan......Drug design of protein kinase inhibitors is now greatly enabled by thousands of publicly available X-ray structures, extensive ligand binding data, and optimized scaffolds coming off patent. The extensive data begin to enable design against a spectrum of targets (polypharmacology); however...... consider polypharmacological targeting of protein kinases ALK, MET, and EGFR (and its drug resistant mutant T790M) in non small cell lung cancer as an example. Both EGFR and ALK represent sources of primary oncogenic lesions, while drug resistance arises from MET amplification and EGFR mutation. A drug...

  3. The Open Form Inducer Approach for Structure-Based Drug Design.

    Directory of Open Access Journals (Sweden)

    Daniel Ken Inaoka

    Full Text Available Many open form (OF structures of drug targets were obtained a posteriori by analysis of co-crystals with inhibitors. Therefore, obtaining the OF structure of a drug target a priori will accelerate development of potent inhibitors. In addition to its small active site, Trypanosoma cruzi dihydroorotate dehydrogenase (TcDHODH is fully functional in its monomeric form, making drug design approaches targeting the active site and protein-protein interactions unrealistic. Therefore, a novel a priori approach was developed to determination the TcDHODH active site in OF. This approach consists of generating an "OF inducer" (predicted in silico to bind the target and cause steric repulsion with flexible regions proximal to the active site that force it open. We provide the first proof-of-concept of this approach by predicting and crystallizing TcDHODH in complex with an OF inducer, thereby obtaining the OF a priori with its subsequent use in designing potent and selective inhibitors. Fourteen co-crystal structures of TcDHODH with the designed inhibitors are presented herein. This approach has potential to encourage drug design against diseases where the molecular targets are such difficult proteins possessing small AS volume. This approach can be extended to study open/close conformation of proteins in general, the identification of allosteric pockets and inhibitors for other drug targets where conventional drug design approaches are not applicable, as well as the effective exploitation of the increasing number of protein structures deposited in Protein Data Bank.

  4. Molecular dynamics in drug design: new generations of compstatin analogs.

    Science.gov (United States)

    Tamamis, Phanourios; López de Victoria, Aliana; Gorham, Ronald D; Bellows-Peterson, Meghan L; Pierou, Panayiota; Floudas, Christodoulos A; Morikis, Dimitrios; Archontis, Georgios

    2012-05-01

    We report the computational and rational design of new generations of potential peptide-based inhibitors of the complement protein C3 from the compstatin family. The binding efficacy of the peptides is tested by extensive molecular dynamics-based structural and physicochemical analysis, using 32 atomic detail trajectories in explicit water for 22 peptides bound to human, rat or mouse target protein C3, with a total of 257 ns. The criteria for the new design are: (i) optimization for C3 affinity and for the balance between hydrophobicity and polarity to improve solubility compared to known compstatin analogs; and (ii) development of dual specificity, human-rat/mouse C3 inhibitors, which could be used in animal disease models. Three of the new analogs are analyzed in more detail as they possess strong and novel binding characteristics and are promising candidates for further optimization. This work paves the way for the development of an improved therapeutic for age-related macular degeneration, and other complement system-mediated diseases, compared to known compstatin variants. © 2012 John Wiley & Sons A/S.

  5. New designer drugs (synthetic cannabinoids and synthetic cathinones): review of literature.

    Science.gov (United States)

    Cottencin, Olivier; Rolland, Benjamin; Karila, Laurent

    2014-01-01

    New designer drugs (synthetic cannabinoids and synthetic cathinones) are new "legal highs" that are sold online for recreational public or private use. Synthetic cannabinoids are psychoactive herbal and chemical products that mimic the effects of cannabis when used. These drugs are available on the Internet or in head shops as incense or air fresheners to circumvent the law. Cathinone is a naturally occurring beta-ketone amphetamine analog found in the leaves of the Catha edulis plant. Synthetic cathinones are phenylalkylamine derivatives that may possess amphetamine-like properties. These drugs are sold online as bath salts. Designer drugs are often labeled as "not for human consumption" to circumvent drug abuse legislation. The absence of legal risks, the ease of obtaining these drugs, the moderate cost, and the availability via the Internet are the main features that attract users, but the number of intoxicated people presenting with emergencies is increasing. There is evidence that negative health and social consequences may affect recreational and chronic users. The addictive potential of designer drugs is not negligible.

  6. Multi-Step Usage of in Vivo Models During Rational Drug Design and Discovery

    Directory of Open Access Journals (Sweden)

    Charles H. Williams

    2011-04-01

    Full Text Available In this article we propose a systematic development method for rational drug design while reviewing paradigms in industry, emerging techniques and technologies in the field. Although the process of drug development today has been accelerated by emergence of computational methodologies, it is a herculean challenge requiring exorbitant resources; and often fails to yield clinically viable results. The current paradigm of target based drug design is often misguided and tends to yield compounds that have poor absorption, distribution, metabolism, and excretion, toxicology (ADMET properties. Therefore, an in vivo organism based approach allowing for a multidisciplinary inquiry into potent and selective molecules is an excellent place to begin rational drug design. We will review how organisms like the zebrafish and Caenorhabditis elegans can not only be starting points, but can be used at various steps of the drug development process from target identification to pre-clinical trial models. This systems biology based approach paired with the power of computational biology; genetics and developmental biology provide a methodological framework to avoid the pitfalls of traditional target based drug design.

  7. Protein-Protein Docking in Drug Design and Discovery.

    Science.gov (United States)

    Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

    2018-01-01

    Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

  8. Transactions in Desire: Media Imaginings of Narcotics and Terrorism in Indonesia

    Directory of Open Access Journals (Sweden)

    Jeff Lewis

    2010-09-01

    Full Text Available The relationship between Australia (an outpost of Anglo-western culture and Indonesia (the world's most populous Muslim nation has always been precarious. Much of the Australian media and political 'mediasphere' have contributed to the destabilisation of this relationship, most particularly as many media professionals reduce complex transcultural and transnational engagement to simple and essentialised cultural dichotomies. This limited vision is evident in the popular media's treatment of two significant politico-cultural issues: regional terrorism and the trade in illicit narcotics. Within a context of the global war on terror and Islamic attacks in Bali, much of the Australian popular media and public have been particularly agitated by the conviction and death sentencing of a group of Australians (the Bali Nine who had attempted to smuggle heroin out of Indonesia. This article examines the interrelationship between drug trafficking and regional security in South East Asia, most specifically as the issues have been conflated through transnational politics and the Australian media. The article concludes that these issues have a common trajectory within the momentum of globalisation and the cultural imaginaries created through the modern mediasphere.

  9. Transactions in desire : media imaginings of narcotics and terrorism in Indonesia

    Directory of Open Access Journals (Sweden)

    Lewis, Jeff

    2010-01-01

    Full Text Available The relationship between Australia (an outpost of Anglo-western culture and Indonesia (the world's most populous Muslim nation has always been precarious. Much of the Australian media and political 'mediasphere' have contributed to the destabilisation of this relationship, most particularly as many media professionals reduce complex transcultural and transnational engagement to simple and essentialised cultural dichotomies. This limited vision is evident in the popular media's treatment of two significant politico-cultural issues: regional terrorism and the trade in illicit narcotics. Within a context of the global war on terror and Islamic attacks in Bali, much of the Australian popular media and public have been particularly agitated by the conviction and death sentencing of a group of Australians (the Bali Nine who had attempted to smuggle heroin out of Indonesia. This article examines the interrelationship between drug trafficking and regional security in South East Asia, most specifically as the issues have been conflated through transnational politics and the Australian media. The article concludes that these issues have a common trajectory within the momentum of globalisation and the cultural imaginaries created through the modern mediasphere.

  10. Optimization and design of ibuprofen-loaded nanostructured lipid carriers using a hybrid-design approach for ocular drug delivery

    Science.gov (United States)

    Rathod, Vishal

    The objective of the present project was to develop the Ibuprofen-loaded Nanostructured Lipid Carrier (IBU-NLCs) for topical ocular delivery based on substantial pre-formulation screening of the components and understanding the interplay between the formulation and process variables. The BCS Class II drug: Ibuprofen was selected as the model drug for the current study. IBU-NLCs were prepared by melt emulsification and ultrasonication technique. Extensive pre-formulation studies were performed to screen the lipid components (solid and liquid) based on drug's solubility and affinity as well as components compatibility. The results from DSC & XRD assisted in selecting the most suitable ratio to be utilized for future studies. DynasanRTM 114 was selected as the solid lipid & MiglyolRTM 840 was selected as the liquid lipid based on preliminary lipid screening. The ratio of 6:4 was predicted to be the best based on its crystallinity index and the thermal events. As there are many variables involved for further optimization of the formulation, a single design approach is not always adequate. A hybrid-design approach was applied by employing the Plackett Burman design (PBD) for preliminary screening of 7 critical variables, followed by Box-Behnken design (BBD), a sub-type of response surface methodology (RSM) design using 2 relatively significant variables from the former design and incorporating Surfactant/Co-surfactant ratio as the third variable. Comparatively, KolliphorRTM HS15 demonstrated lower Mean Particle Size (PS) & Polydispersity Index (PDI) and KolliphorRTM P188 resulted in Zeta Potential (ZP) ibuprofen thereafter over several hours. These values also confirm that the production method, and all other selected variables, effectively promoted the incorporation of ibuprofen in NLC. Quality by Design (QbD) approach was successfully implemented in developing a robust ophthalmic formulation with superior physicochemical and morphometric properties. NLCs as the

  11. Site Identification by Ligand Competitive Saturation (SILCS) Simulations for Fragment-Based Drug Design

    OpenAIRE

    Faller, Christina E.; Raman, E. Prabhu; MacKerell, Alexander D.; Guvench, Olgun

    2015-01-01

    Fragment-based drug design (FBDD) involves screening low molecular weight molecules (“fragments”) that correspond to functional groups found in larger drug-like molecules to determine their binding to target proteins or nucleic acids. Based on the principle of thermodynamic additivity, two fragments that bind non-overlapping nearby sites on the target can be combined to yield a new molecule whose binding free energy is the sum of those of the fragments. Experimental FBDD approaches, like NMR ...

  12. Versatile Chemical Derivatizations to Design Glycol Chitosan-Based Drug Carriers

    Directory of Open Access Journals (Sweden)

    Sung Eun Kim

    2017-10-01

    Full Text Available Glycol chitosan (GC and its derivatives have been extensively investigated as safe and effective drug delivery carriers because of their unique physiochemical and biological properties. The reactive functional groups such as the amine and hydroxyl groups on the GC backbone allow for easy chemical modification with various chemical compounds (e.g., hydrophobic molecules, crosslinkers, and acid-sensitive and labile molecules, and the versatility in chemical modifications enables production of a wide range of GC-based drug carriers. This review summarizes the versatile chemical modification methods that can be used to design GC-based drug carriers and describes their recent applications in disease therapy.

  13. Quantum mechanics implementation in drug-design workflows: does it really help?

    Science.gov (United States)

    Arodola, Olayide A; Soliman, Mahmoud Es

    2017-01-01

    The pharmaceutical industry is progressively operating in an era where development costs are constantly under pressure, higher percentages of drugs are demanded, and the drug-discovery process is a trial-and-error run. The profit that flows in with the discovery of new drugs has always been the motivation for the industry to keep up the pace and keep abreast with the endless demand for medicines. The process of finding a molecule that binds to the target protein using in silico tools has made computational chemistry a valuable tool in drug discovery in both academic research and pharmaceutical industry. However, the complexity of many protein-ligand interactions challenges the accuracy and efficiency of the commonly used empirical methods. The usefulness of quantum mechanics (QM) in drug-protein interaction cannot be overemphasized; however, this approach has little significance in some empirical methods. In this review, we discuss recent developments in, and application of, QM to medically relevant biomolecules. We critically discuss the different types of QM-based methods and their proposed application to incorporating them into drug-design and -discovery workflows while trying to answer a critical question: are QM-based methods of real help in drug-design and -discovery research and industry?

  14. A comparison of intraoperative morphine sulfate and methadone hydrochloride on postoperative visual analogue scale pain scores and narcotic requirements.

    Science.gov (United States)

    Laur, D F; Sinkovich, J; Betley, K

    1995-02-01

    Morphine sulfate and methadone hydrochloride exhibit very different half-lives but are described as having an analgesic potency of one. The use of a drug like methadone may provide prolonged and constant analgesia in the perioperative setting. This double-blinded investigation used methadone and morphine intraoperatively and measured pain scores and narcotic requirements in the first 24 hours postoperatively. Thirty American Society of Anesthesiology (ASA) patients, physical status I through III, between the ages of 18 to 65 years were scheduled for orthopedic surgery and randomly assigned to receive morphine or methadone at 0.30 mg/kg. Fifteen patients received morphine and fifteen patients received methadone. There was no significant difference between the two groups in terms of age, height, weight, and ASA status. No statistically significant difference was observed among the two groups between the amount of analgesic requirements postoperatively or in the visual analogue scale pain score.

  15. Ebola virus: A gap in drug design and discovery - experimental and computational perspective.

    Science.gov (United States)

    Balmith, Marissa; Faya, Mbuso; Soliman, Mahmoud E S

    2017-03-01

    The Ebola virus, formally known as the Ebola hemorrhagic fever, is an acute viral syndrome causing sporadic outbreaks that have ravaged West Africa. Due to its extreme virulence and highly transmissible nature, Ebola has been classified as a category A bioweapon organism. Only recently have vaccine or drug regimens for the Ebola virus been developed, including Zmapp and peptides. In addition, existing drugs which have been repurposed toward anti-Ebola virus activity have been re-examined and are seen to be promising candidates toward combating Ebola. Drug development involving computational tools has been widely employed toward target-based drug design. Screening large libraries have greatly stimulated research toward effective anti-Ebola virus drug regimens. Current emphasis has been placed on the investigation of host proteins and druggable viral targets. There is a huge gap in the literature regarding guidelines in the discovery of Ebola virus inhibitors, which may be due to the lack of information on the Ebola drug targets, binding sites, and mechanism of action of the virus. This review focuses on Ebola virus inhibitors, drugs which could be repurposed to combat the Ebola virus, computational methods which study drug-target interactions as well as providing further insight into the mode of action of the Ebola virus. © 2016 John Wiley & Sons A/S.

  16. Using computer-aided drug design and medicinal chemistry strategies in the fight against diabetes.

    Science.gov (United States)

    Semighini, Evandro P; Resende, Jonathan A; de Andrade, Peterson; Morais, Pedro A B; Carvalho, Ivone; Taft, Carlton A; Silva, Carlos H T P

    2011-04-01

    The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics, ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.

  17. Design optimization of a novel pMDI actuator for systemic drug delivery.

    Science.gov (United States)

    Kakade, Prashant P; Versteeg, Henk K; Hargrave, Graham K; Genova, Perry; Williams Iii, Robert C; Deaton, Daniel

    2007-01-01

    Pressurized metered dose inhalers (pMDIs) are the most widely prescribed and economical respiratory drug delivery systems. Conventional pMDI actuators-those based on "two-orifice-and-sump" designs-produce an aerosol with a reasonable respirable fraction, but with high aerosol velocity. The latter is responsible for high oropharyngeal deposition, and consequently low drug delivery efficiency. Kos' pMDI technology is based on a proprietary vortex nozzle actuator (VNA), an innovative actuator configuration that seeks to reduce aerosol plume velocity, thereby promoting deep lung deposition. Using VNA development as a case study, this paper presents a systematic design optimization process to improve the actuator performance through use of advanced optical characterization tools. The optimization effort mainly relied on laser-based optical diagnostics to provide an improved understanding of the fundamentals of aerosol formation and interplay of various geometrical factors. The performance of the optimized VNA design thus evolved was characterized using phase Doppler anemometry and cascade impaction. The aerosol velocities for both standard and optimized VNA designs were found to be comparable, with both notably less than conventional actuators. The optimized VNA design also significantly reduces drug deposition in the actuator as well as USP throat adapter, which in turn, leads to a significantly higher fine particle fraction than the standard design (78 +/- 3% vs. 63 +/- 2% on an ex valve basis). This improved drug delivery efficiency makes VNA technology a practical proposition as a systemic drug delivery platform. Thus, this paper demonstrates how advanced optical diagnostic and characterization tools can be used in the development of high efficiency aerosol drug delivery devices.

  18. The gastrointestinal tract as a vehicle for drug smuggling

    International Nuclear Information System (INIS)

    Sinner, W.N.

    1981-01-01

    Four cases of attempts to smuggle narcotics (marijuana, heroin, and cocaine) by swallowing a large number of drug-filled foreign bodies (condoms and capsules) and hiding them from customs authorities in the gastrointestinal canal during transit are described. This is compared with a psychiatric patient who swallowed 48 Vicks Inhalers. Drug smuggling by swallowing condoms or capsules containing narcotics is now a worldwide ethical-legal problem. It also is of therapeutic and prognostic importance as this may lead to such emergencies as mechanical obstruction, rupture of the drug-containing foreign bodies, and life-threatening intoxication of the carrier. (orig.)

  19. Gastrointestinal tract as a vehicle for drug smuggling

    Energy Technology Data Exchange (ETDEWEB)

    Sinner, W.N.

    1981-10-15

    Four cases of attempts to smuggle narcotics (marijuana, heroin, and cocaine) by swallowing a large number of drug-filled foreign bodies (condoms and capsules) and hiding them from customs authorities in the gastrointestinal canal during transit are described. This is compared with a psychiatric patient who swallowed 48 Vicks Inhalers. Drug smuggling by swallowing condoms or capsules containing narcotics is now a worldwide ethical-legal problem. It also is of therapeutic and prognostic importance as this may lead to such emergencies as mechanical obstruction, rupture of the drug-containing foreign bodies, and life-threatening intoxication of the carrier.

  20. Deep Learning for Drug Design: an Artificial Intelligence Paradigm for Drug Discovery in the Big Data Era.

    Science.gov (United States)

    Jing, Yankang; Bian, Yuemin; Hu, Ziheng; Wang, Lirong; Xie, Xiang-Qun Sean

    2018-03-30

    Over the last decade, deep learning (DL) methods have been extremely successful and widely used to develop artificial intelligence (AI) in almost every domain, especially after it achieved its proud record on computational Go. Compared to traditional machine learning (ML) algorithms, DL methods still have a long way to go to achieve recognition in small molecular drug discovery and development. And there is still lots of work to do for the popularization and application of DL for research purpose, e.g., for small molecule drug research and development. In this review, we mainly discussed several most powerful and mainstream architectures, including the convolutional neural network (CNN), recurrent neural network (RNN), and deep auto-encoder networks (DAENs), for supervised learning and nonsupervised learning; summarized most of the representative applications in small molecule drug design; and briefly introduced how DL methods were used in those applications. The discussion for the pros and cons of DL methods as well as the main challenges we need to tackle were also emphasized.

  1. Study on optimization design of superconducting magnet for magnetic force assisted drug delivery system

    International Nuclear Information System (INIS)

    Fukui, S.; Abe, R.; Ogawa, J.; Oka, T.; Yamaguchi, M.; Sato, T.; Imaizumi, H.

    2007-01-01

    Analytical study on the design of the superconducting magnet for the magnetic force assisted drug delivery system is presented in this paper. The necessary magnetic field condition to reside the magnetic drug particle in the blood vessels is determined by analyzing the particle motion in the blood vessel. The design procedure of the superconducting magnet for the M-DDS is presented and some case studies are conducted. The analytical results show that the superconducting magnet to satisfy the magnetic field conduction for the M-DDS is practically feasible

  2. Continuous Drug Infusion for Diabetes Therapy: A Closed-Loop Control System Design

    Directory of Open Access Journals (Sweden)

    Jiming Chen

    2008-03-01

    Full Text Available While a typical way for diabetes therapy is discrete insulin infusion based on long-time interval measurement, in this paper, we design a closed-loop control system for continuous drug infusion to improve the traditional discrete methods and make diabetes therapy automatic in practice. By exploring the accumulative function of drug to insulin, a continuous injection model is proposed. Based on this model, proportional-integral-derivative (PID and fuzzy logic controllers are designed to tackle a control problem of the resulting highly nonlinear plant. Even with serious disturbance of glucose, such as nutrition absorption at meal time, the proposed scheme can perform well in simulation experiments.

  3. An Optimization Model for Expired Drug Recycling Logistics Networks and Government Subsidy Policy Design Based on Tri-level Programming

    OpenAIRE

    Huang, Hui; Li, Yuyu; Huang, Bo; Pi, Xing

    2015-01-01

    In order to recycle and dispose of all people’s expired drugs, the government should design a subsidy policy to stimulate users to return their expired drugs, and drug-stores should take the responsibility of recycling expired drugs, in other words, to be recycling stations. For this purpose it is necessary for the government to select the right recycling stations and treatment stations to optimize the expired drug recycling logistics network and minimize the total costs of recycling and disp...

  4. Mexico's "ley de narcomenudeo" drug policy reform and the international drug control regime.

    Science.gov (United States)

    Mackey, Tim K; Werb, Daniel; Beletsky, Leo; Rangel, Gudelia; Arredondo, Jaime; Strathdee, Steffanie A

    2014-11-14

    It has been over half a century since the landmark Single Convention on Narcotic Drugs was adopted, for the first time unifying international drug policy under a single treaty aimed at limiting use, manufacture, trade, possession, and trafficking of opiates, cannabis, and other narcotics. Since then, other international drug policy measures have been adopted, largely emphasizing enforcement-based approaches to reducing drug supply and use. Recently, in response to concerns that the historic focus on criminalization and enforcement has had limited effectiveness, international drug policies have begun to undergo a paradigm shift as countries seek to enact their own reforms to partially depenalize or deregulate personal drug use and possession. This includes Mexico, which in 2009 enacted national drug policy reform partially decriminalizing possession of small quantities of narcotics for personal consumption while also requiring drug treatment for repeat offenders. As countries move forward with their own reform models, critical assessment of their legal compatibility and effectiveness is necessary. In this commentary we conduct a critical assessment of the compatibility of Mexico's reform policy to the international drug policy regime and describe its role in the current evolving drug policy environment. We argue that Mexico's reform is consistent with flexibilities allowed under international drug treaty instruments and related commentaries. We also advocate that drug policy reforms and future governance efforts should be based on empirical evidence, emphasize harm reduction practices, and integrate evidence-based evaluation and implementation of drug reform measures.

  5. Medicinal Chemistry Projects Requiring Imaginative Structure-Based Drug Design Methods.

    Science.gov (United States)

    Moitessier, Nicolas; Pottel, Joshua; Therrien, Eric; Englebienne, Pablo; Liu, Zhaomin; Tomberg, Anna; Corbeil, Christopher R

    2016-09-20

    Computational methods for docking small molecules to proteins are prominent in drug discovery. There are hundreds, if not thousands, of documented examples-and several pertinent cases within our research program. Fifteen years ago, our first docking-guided drug design project yielded nanomolar metalloproteinase inhibitors and illustrated the potential of structure-based drug design. Subsequent applications of docking programs to the design of integrin antagonists, BACE-1 inhibitors, and aminoglycosides binding to bacterial RNA demonstrated that available docking programs needed significant improvement. At that time, docking programs primarily considered flexible ligands and rigid proteins. We demonstrated that accounting for protein flexibility, employing displaceable water molecules, and using ligand-based pharmacophores improved the docking accuracy of existing methods-enabling the design of bioactive molecules. The success prompted the development of our own program, Fitted, implementing all of these aspects. The primary motivation has always been to respond to the needs of drug design studies; the majority of the concepts behind the evolution of Fitted are rooted in medicinal chemistry projects and collaborations. Several examples follow: (1) Searching for HDAC inhibitors led us to develop methods considering drug-zinc coordination and its effect on the pKa of surrounding residues. (2) Targeting covalent prolyl oligopeptidase (POP) inhibitors prompted an update to Fitted to identify reactive groups and form bonds with a given residue (e.g., a catalytic residue) when the geometry allows it. Fitted-the first fully automated covalent docking program-was successfully applied to the discovery of four new classes of covalent POP inhibitors. As a result, efficient stereoselective syntheses of a few screening hits were prioritized rather than synthesizing large chemical libraries-yielding nanomolar inhibitors. (3) In order to study the metabolism of POP inhibitors by

  6. [The War on "Red Drugs": Anticommunism and Drug Policy in Republic of Korea, 1945-1960].

    Science.gov (United States)

    Park, Ji-Young

    2016-04-01

    This paper investigates the discourses and policies on narcotics in Republic of Korea from 1945 to 1960. Since the Liberation the narcotic problem was regarded as the vestige of Japanese imperialism. which was expected to be cleaned up. The image of narcotic crimes as the legacy of the colonial past was turned into as the result of the Red Army's tactics to attack on the liberalist camp around the Korean war. The government of ROK represented the source of the illegal drugs as the Red army and the spy from North Korea. The anticommunist discourse about narcotics described the spies, who introduced the enormous amount of poppies into ROK and brought about the addicts, as the social evil. Through this discourse on poppies from North Korea, the government of ROK emphasized the immorality of the communists reinforcing the anticommunist regime, which was inevitable for the government of ROK to legitimize the division of Korea and the establishment of the government alone. This paper examines how the discourses and policies on narcotics in ROK was shaped and transformed from 1945 to 1960 focusing the relationship between the them and the political context such as anticommunism, Korean war, the division of Korea, and etc. This approach would be helpful to reveal the effect of the ROK's own political situation to the public health system involving the management for drugs.

  7. Molecular docking as a popular tool in drug design, an in silico travel

    Directory of Open Access Journals (Sweden)

    de Ruyck J

    2016-06-01

    Full Text Available Jerome de Ruyck, Guillaume Brysbaert, Ralf Blossey, Marc F Lensink University Lille, CNRS UMR8576 UGSF, Lille, FranceAbstract: New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism- or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein–protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery.Keywords: structure-based drug design, protein–protein docking, quaternary structure prediction, residue interaction networks, RINs, water position

  8. Design and fabrication of a magnetically actuated non-invasive reusable drug delivery device.

    Science.gov (United States)

    Dsa, Joyline; Goswami, Manish; Singh, B R; Bhatt, Nidhi; Sharma, Pankaj; Chauhan, Meenakshi K

    2018-07-01

    We present a novel approach of designing and fabricating a noninvasive drug delivery device which is capable of delivering the drug to the target site in a controlled manner. The device utilizes a reservoir which can be reused once the drug has completely diffused from it. This micro-reservoir based fabricated device has been successfully tested using niosomes of insulin drug filled in, which was then sealed with a magnetic membrane of 20 µm thick and was actuated by applying magnetic field. The deflection of the membrane on application of magnetic field results in the drug release from the reservoir. The discharge of the drug solution and the release rates was controlled by external magnetic field. The simulation of the membrane deflection using COMSOL software was carried out to optimize the concentration of the ferrous nanopowder in PDMS matrix. The characterization of the devices was implemented in-vitro on water and in-vivo on Wistar rats. It was also validated using high-performance liquid chromatography (HPLC) by observing characteristic peak of insulin. The blood samples showed the retention time of 2.79 min at λ max of 280 nm which further authenticated the effectiveness of the proposed work. This noninvasive fabricated device provides reusability, precise control and can enable the patient or a physician to actively administrate the drug when required.

  9. Price Sensitivity of Demand for Prescription Drugs: Exploiting a Regression Kink Design

    DEFF Research Database (Denmark)

    Simonsen, Marianne; Skipper, Lars; Skipper, Niels

    This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression ...... education and income are, however, more responsive to the price. Also, essential drugs that prevent deterioration in health and prolong life have lower associated average price sensitivity....... kink design. Thus, within a unifying framework we uncover price sensitivity for different subpopulations and types of drugs. The results suggest low average price responsiveness with corresponding price elasticities ranging from -0.08 to -0.25, implying that demand is inelastic. Individuals with lower...

  10. Bio-Inspired Multi-Functional Drug Transport Design Concept and Simulations.

    Science.gov (United States)

    Pidaparti, Ramana M; Cartin, Charles; Su, Guoguang

    2017-04-25

    In this study, we developed a microdevice concept for drug/fluidic transport taking an inspiration from supramolecular motor found in biological cells. Specifically, idealized multi-functional design geometry (nozzle/diffuser/nozzle) was developed for (i) fluidic/particle transport; (ii) particle separation; and (iii) droplet generation. Several design simulations were conducted to demonstrate the working principles of the multi-functional device. The design simulations illustrate that the proposed design concept is feasible for multi-functionality. However, further experimentation and optimization studies are needed to fully evaluate the multifunctional device concept for multiple applications.

  11. Molecular Thermodynamic Modeling and Design of Microencapsulation Systems for Drug Delivery

    DEFF Research Database (Denmark)

    Abildskov, Jens; O’Connell, John P.

    2011-01-01

    is based on fundamental thermodynamic relations and group contributions to properties of pure species (solvent, active ingredient and polymer) and their mixtures. The method is intended for pharmaceuticals with complex molecular structures, for which limited experimental information is known. Case studies......A systematic design strategy is given for computer-aided design of microparticle drug-delivery systems produced by solvent evaporation. In particular, design of solvents, polymer material, and external phase composition are considered for the case when the active ingredient is known. The procedure...... of solvent design are given....

  12. Return to Galileo? The Inquisition of the International Narcotic Control Board.

    Science.gov (United States)

    Small, Dan; Drucker, Ernest

    2008-05-07

    Nearly 400 years after Galileo Galilei of Florence was arraigned and convicted of suspected heresy by the ten member Congregation of the Holy Office (Inquisition), the International Narcotic Control Board (INCB) is similarly inserting itself into matters pertaining to innovations in healthcare and the public health response to addiction throughout the world. Like that earlier Inquisition of 1633 that convicted Galileo of heresy for holding that the sun is the centre of the universe with the earth revolving around it (in contradiction to church doctrine of the time) the INCB and its thirteen-member panel, now rails against any evidence out of sync with the established doctrine of the war on drugs--particularly those innovations in public health called harm reduction. The latest healthcare and harm reduction practices to attract the ire of the INCB Inquisition are elements of Canada's most effective and innovative measures to minimize the harms of drugs in Vancouver--supervised injection facilities and, recently, the potential establishment of supervised inhalation rooms--along with the long established practice of providing safer mouthpieces for pulmonary inhalation in British Columbia. This is particularly significant as it comes in the midst of a crucial battle between municipal and provincial authorities in BC with the federal government in Ottawa, which seems determined to undermine all the most effective HR programs that are the result of years of steady local and governmental support in Vancouver and now threatens to derail all these programs and spread doubt about their usefulness despite the overwhelmingly positive findings of serous research.

  13. Return to Galileo? The Inquisition of the International Narcotic Control Board

    Directory of Open Access Journals (Sweden)

    Small Dan

    2008-05-01

    Full Text Available Abstract Nearly 400 years after Galileo Galilei of Florence was arraigned and convicted of suspected heresy by the ten member Congregation of the Holy Office (Inquisition, the International Narcotic Control Board (INCB is similarly inserting itself into matters pertaining to innovations in healthcare and the public health response to addiction throughout the world. Like that earlier Inquisition of 1633 that convicted Galileo of heresy for holding that the sun is the centre of the universe with the earth revolving around it (in contradiction to church doctrine of the time the INCB and its thirteen-member panel, now rails against any evidence out of sync with the established doctrine of the war on drugs – particularly those innovations in public health called harm reduction. The latest healthcare and harm reduction practices to attract the ire of the INCB Inquisition are elements of Canada's most effective and innovative measures to minimize the harms of drugs in Vancouver – supervised injection facilities and, recently, the potential establishment of supervised inhalation rooms – along with the long established practice of providing safer mouthpieces for pulmonary inhalation in British Columbia. This is particularly significant as it comes in the midst of a crucial battle between municipal and provincial authorities in BC with the federal government in Ottawa, which seems determined to undermine all the most effective HR programs that are the result of years of steady local and governmental support in Vancouver and now threatens to derail all these programs and spread doubt about their usefulness despite the overwhelmingly positive findings of serous research.

  14. Pill testing or drug checking in Australia: Acceptability of service design features.

    Science.gov (United States)

    Barratt, Monica J; Bruno, Raimondo; Ezard, Nadine; Ritter, Alison

    2018-02-01

    This study aimed to determine design features of a drug-checking service that would be feasible, attractive and likely to be used by Australian festival and nightlife attendees. Web survey of 851 Australians reporting use of psychostimulants and/or hallucinogens and attendance at licensed venues past midnight and/or festivals in the past year (70% male; median age 23 years). A drug-checking service located at festivals or clubs would be used by 94%; a fixed-site service external to such events by 85%. Most (80%) were willing to wait an hour for their result. Almost all (94%) would not use a service if there was a possibility of arrest, and a majority (64%) would not use a service that did not provide individual feedback of results. Drug-checking results were only slightly more attractive if they provided comprehensive quantitative results compared with qualitative results of key ingredients. Most (93%) were willing to pay up to $5, and 68% up to $10, per test. One-third (33%) reported willingness to donate a whole dose for testing: they were more likely to be male, younger, less experienced, use drugs more frequently and attend venues/festivals less frequently. In this sample, festival- or club-based drug-checking services with low wait times and low cost appear broadly attractive under conditions of legal amnesty and individualised feedback. Quantitative analysis of ecstasy pills requiring surrender of a whole pill may appeal to a minority in Australia where pills are more expensive than elsewhere. [Barratt MJ, Bruno R, Ezard N, Ritter A. Pill testing or drug checking in Australia: Acceptability of service design features. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  15. Drugs and Minorities. Research Issues 21.

    Science.gov (United States)

    Austin, Gregory A., Ed.; And Others

    This volume contains summaries of the latest research focusing on the issue of the extent of drug use and abuse among racial and ethnic minorities and the factors influencing it. Taken into consideration are age and sex differences among users, narcotics addiction, socioeconomic influences, cultural factors, racial factors, demographic factors,…

  16. 10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

    Science.gov (United States)

    2010-01-01

    ... contractor, to have the potential to significantly affect the environment, public health and safety, or... evidence of the use of illegal drugs of employees in testing designated positions identified in this... section shall provide for random tests at a rate equal to 30 percent of the total number of employees in...

  17. Elucidating Concepts in Drug Design through Taste with Natural and Artificial Sweeteners

    Science.gov (United States)

    Lipchock, James M.; Lipchock, Sarah V.

    2016-01-01

    Fundamental concepts in biochemistry important for drug design often lack connection to the macroscopic world and can be difficult for students to grasp, particularly those in introductory science courses at the high school and college level. Educational research has shown that multisensory teaching facilitates learning, but teaching at the high…

  18. 21 CFR 516.30 - Annual reports for a MUMS-designated drug.

    Science.gov (United States)

    2010-04-01

    ... status or results of such studies; (b) A description of the investigational plan for the coming year, as well as any anticipated difficulties in development, testing, and marketing; and (c) A brief discussion of any changes that may affect the MUMS-designated drug status of the product. For example...

  19. The semiempirical quantum mechanical scoring function for in-silico drug design

    Czech Academy of Sciences Publication Activity Database

    Fanfrlík, Jindřich; Lepšík, Martin; Řezáč, Jan; Kolář, Michal; Pecina, Adam; Nachtigallová, Dana; Hobza, Pavel

    2015-01-01

    Roč. 22, č. 1 (2015), s. 34 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] Institutional support: RVO:61388963 Keywords : drug design * SQM methods * binding Subject RIV: CF - Physical ; Theoretical Chemistry

  20. The role of illicit, licit, and designer drugs in the traffic in Hungary.

    Science.gov (United States)

    Institóris, László; Hidvégi, Előd; Dobos, Adrienn; Sija, Éva; Kereszty, Éva M; Tajti, László Balázs; Somogyi, Gábor Pál; Varga, Tibor

    2017-06-01

    The aim of this study was to investigate the prevalence and pattern of psychoactive substances among suspected DUID (Driving Under the Influence of Drugs) drivers in Hungary in 2014 and 2015. Blood and/or urine samples of 1252 suspected drivers (600 in 2014 and 652 in 2015) were analyzed for classical illicit and licit drugs, stimulant designer drugs (SDDs), and for synthetic cannabinoids, with 78.3% and 79.6% positive cases for at least one substance in 2014, and 2015, respectively. Impairment was proven in 39.2% (2014) and 35.7% (2015) of all drivers tested, based on the legal criteria of Hungary. Classical illicit drugs were found to be present in blood or urine of 89-61%, drivers tested. Drivers also tested positive for legal medications in 20-22%, SDDs in 21-28%, and synthetic cannabinoids in 15-19% of all cases. This indicates a drop in prevalence for classical illicit drugs and a slight but statistically non-significant increase for the other three substance groups. The distribution of drug types in each category were: [1] classical illicit drugs: cannabis (432), amphetamine (321), and cocaine (79); [2] medicines: alprazolam (94) and clonazepam (36); [3] SDDs: pentedrone (137) and α-PVP (33); [4] synthetic cannabinoids: AB-CHMINACA (46) and MDMB-CHMICA (30). The average age of illicit drug and SDD users was 30 years, while legal medications users were 36 years old on average, and the mean age of synthetic cannabinoid users was 26.5 years. The presence of both alcohol and at least one drug in samples was found in about 10% of the cases, both years. The ratio of multi-drug use was 33.0% in 2014 and 41.3% in 2015. Compared to former years the number of drivers who tested positive for drugs doubled in Hungary, but it is still low compared to alcohol positive cases. The relatively low detected rate of DUID can be explained by (1) combined alcohol consumption masking drug symptoms, (2) the absence of road-side tests for illicit and designer drugs and, (3) police

  1. Design of Drug Delivery Methods for the Brain and Central Nervous System

    Science.gov (United States)

    Lueshen, Eric

    Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection

  2. Identification of designer drug 2C-E (4-ethyl-2, 5-dimethoxy-phenethylamine) in urine following a drug overdose

    OpenAIRE

    Van Vrancken, Michael J.; Benavides, Raul; Wians, Frank H.

    2013-01-01

    In recent years, access to information regarding acquisition and synthesis of newer designer drugs has been at an all-time high due largely to the Internet. As these drugs have become more prevalent, laboratory techniques have been developed and refined to identify and screen for this burgeoning population of drugs. This provides a unique opportunity for learning about many of these methods. Laboratory testing techniques and instrumentation are obscure to many health care professionals, yet t...

  3. The Dutch drug policy from a regulatory perspective

    NARCIS (Netherlands)

    Spapens, A.C.M.; Müller, T.; Van de Bunt, H.G.

    2015-01-01

    Starting in the 1970s, the Netherlands developed a regulatory regime for narcotic drugs by distinguishing between hashish and marihuana (“soft drugs”) and other drugs (“hard drugs”). The authorities decided to cease prosecuting the possession of consumer quantities of the former type and to allow

  4. 32 CFR 147.10 - Guideline H-Drug involvement.

    Science.gov (United States)

    2010-07-01

    ... Controlled Substances Act of 1970, as amended (e.g., marijuana or cannabis, depressants, narcotics... use of a drug or use of a legal drug in a manner that deviates from approved medical direction. (b..., sale, or distribution; (3) Diagnosis by a credentialed medical professional (e.g., physician, clinical...

  5. Design and mechanistic study of a novel gold nanocluster-based drug delivery system.

    Science.gov (United States)

    Li, Qinzhen; Pan, Yiting; Chen, Tiankai; Du, Yuanxin; Ge, Honghua; Zhang, Buchang; Xie, Jianping; Yu, Haizhu; Zhu, Manzhou

    2018-05-22

    Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide. The Van-loaded Au NCs show comparable antimicrobial activity with Van on its own, and the number of Van released by the Pep-Au NCs is found to be proportional to the amount of bacteria present. The controlled nature of the Van release is very encouraging, and predominantly due to the stronger binding affinity of Van with bacteria than that with Au NCs. In addition, these fluorescent Au NCs could also be used to construct temperature sensors, which enable the in vitro and in vivo bioimaging.

  6. A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

    Science.gov (United States)

    Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

    2011-08-01

    Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

  7. Colon-targeted oral drug delivery systems: design trends and approaches.

    Science.gov (United States)

    Amidon, Seth; Brown, Jack E; Dave, Vivek S

    2015-08-01

    Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

  8. Rational design of dendrimer/lipid nanoassemblies in drug delivery for cancer chemotherapy

    Science.gov (United States)

    Sun, Qihang

    Nanocarriers can minimize the side effects and improve therapeutic efficacy of anticancer drugs. Although some success has been achieved via active or passive drug delivery to tumor cells, the known nanocarriers are far from satisfying therapeutic efficacy expectations. This is because they usually fail in one of the four crucial requirements, that is, to retain drug in blood circulation but release it reliably in tumor cells and to be stealthy in transport in circulation and tumor tissue but sticky upon arrival at the tumor cell. Therefore, the goal of this work is to fabricate nanoassemblies of dendrimers and lipids to address all these challenges. Particularly, nanoassemblies designed and prepared in this work are illustrated to improve the tumor tissue penetration. Examples of dendrimers synthesized in this work are water-insoluble, pH-dependent water-insoluble and water-soluble biodegradable polyester dendrimers. These dendrimers are shown to be encapsulated by commonly used fusogenic and long-circulating lipids to form reliable nanoassemblies. The dendrimer/lipid nanocarriers are used to demonstrate a cascade drug delivery. They are expected to be stable in circulation, due to their appropriately large size, but to release the drug-loaded dendrimers in tumor tissue. The released dendrimers carrying drugs are much smaller and hence expected to have a much deeper penetration throughout the tumor tissue.

  9. Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

    Science.gov (United States)

    Singh, Pankaj Kumar; Negi, Arvind; Gupta, Pawan Kumar; Chauhan, Monika; Kumar, Raj

    2016-08-01

    Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

  10. Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

    Science.gov (United States)

    Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

    2017-08-18

    The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-05-26

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

  12. Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

    Science.gov (United States)

    Logie, Jennifer

    Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P

  13. Crystals of Human Serum Albumin for Use in Genetic Engineering and Rational Drug Design

    Science.gov (United States)

    Carter, Daniel C. (Inventor)

    1994-01-01

    This invention pertains to crystals of serum albumin and processes for growing them. The purpose of the invention is to provide crystals of serum albumin which can be studied to determine binding sites for drugs. Form 2 crystals grow in the monoclinic space P2(sub 1), and possesses the following unit cell constraints: a = 58.9 +/- 7, b = 88.3 +/- 7, c = 60.7 +/- 7, Beta = 101.0 +/- 2 degrees. One advantage of the invention is that it will allow rational drug design

  14. Design and characterisation of matrix tablets of highly water soluble drug

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Prakya

    2012-04-01

    Full Text Available Tramadol HCL is a centrally acting opioid analgesic. Although the drug has a higher plasma half life, the steady state plasma concentration is not achieved with frequent dosing of q.i.d at 6 hour intervals. Therefore, the objective of the present work was to formulate a 100mg strength Tramadol matrix tablets to extend the drug release and thus decrease the dosing frequency and achieve steady state plasma concentration. Initially, preformulation studies were carried out to rule out any incompatibility between the drug and the chosen polymer(s after exposing physical mixtures of the drug and the polymer(s to 40 and deg;C/75% RH for three months. A suitable method was developed for drug estimation at 271nm by a UV double beam spectrophotometer. Next, various batches of tablets were designed using different polymers such as Ethylcellulose, Carnauba wax, HPMC-K100M, Carbopol-974P and Kollidon-SR. Direct compression technique was used except for the formulation containing carnauba wax for which melt granulation was done followed by compression. Formulations F-1 to F-15 contained single polymers in increasing concentrations in drug:polymer ratios of 1:1, 1:2 and 1:3 where it was observed that the drug release extended with increasing polymer concentrations. Carbopol-974P extended drug release better followed by HPMC-K100M and Carnauba wax compared to other polymers. A combination of these polymers was also used at various ratios to get formulations F-16 to F-20 and observed that the polymer combinations controlled drug release better. The type of fillers like lactose and microcrystalline cellulose had no effect on the physiochemical characters as well as on the drug release profiles. The in vitro release data from the best formulation fitted well in Higuchi as well as Peppas model, the and #8216;n and #8217; value, which confirmed that the release mechanism shifted from initial dissolution to later extended diffusion in which both diffusion and erosion

  15. Metabolism-Activated Multitargeting (MAMUT): An Innovative Multitargeting Approach to Drug Design and Development.

    Science.gov (United States)

    Mátyus, Péter; Chai, Christina L L

    2016-06-20

    Multitargeting is a valuable concept in drug design for the development of effective drugs for the treatment of multifactorial diseases. This concept has most frequently been realized by incorporating two or more pharmacophores into a single hybrid molecule. Many such hybrids, due to the increased molecular size, exhibit unfavorable physicochemical properties leading to adverse effects and/or an inappropriate ADME (absorption, distribution, metabolism, and excretion) profile. To avoid this limitation and achieve additional therapeutic benefits, here we describe a novel multitargeting strategy based on the synergistic effects of a parent drug and its active metabolite(s). The concept of metabolism-activated multitargeting (MAMUT) is illustrated using a number of examples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Design of shared unit-dose drug distribution network using multi-level particle swarm optimization.

    Science.gov (United States)

    Chen, Linjie; Monteiro, Thibaud; Wang, Tao; Marcon, Eric

    2018-03-01

    Unit-dose drug distribution systems provide optimal choices in terms of medication security and efficiency for organizing the drug-use process in large hospitals. As small hospitals have to share such automatic systems for economic reasons, the structure of their logistic organization becomes a very sensitive issue. In the research reported here, we develop a generalized multi-level optimization method - multi-level particle swarm optimization (MLPSO) - to design a shared unit-dose drug distribution network. Structurally, the problem studied can be considered as a type of capacitated location-routing problem (CLRP) with new constraints related to specific production planning. This kind of problem implies that a multi-level optimization should be performed in order to minimize logistic operating costs. Our results show that with the proposed algorithm, a more suitable modeling framework, as well as computational time savings and better optimization performance are obtained than that reported in the literature on this subject.

  17. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    Science.gov (United States)

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  18. 21 CFR 1301.73 - Physical security controls for non-practitioners; compounders for narcotic treatment programs...

    Science.gov (United States)

    2010-04-01

    ...; compounders for narcotic treatment programs; manufacturing and compounding areas. 1301.73 Section 1301.73 Food... controls for non-practitioners; compounders for narcotic treatment programs; manufacturing and compounding... unauthorized persons may not enter or leave the area without his knowledge. (c) During the production of...

  19. Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

    Science.gov (United States)

    Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

    2013-01-01

    Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having

  20. Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution.

    Science.gov (United States)

    Clewe, Oskar; Karlsson, Mats O; Simonsson, Ulrika S H

    2015-12-01

    Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs.

  1. Medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and invention of boron tracedrugs as innovative future-architectural drugs.

    Science.gov (United States)

    Hori, Hitoshi; Uto, Yoshihiro; Nakata, Eiji

    2010-09-01

    We describe herein for the first time our medicinal electronomics bricolage design of hypoxia-targeting antineoplastic drugs and boron tracedrugs as newly emerging drug classes. A new area of antineoplastic drugs and treatments has recently focused on neoplastic cells of the tumor environment/microenvironment involving accessory cells. This tumor hypoxic environment is now considered as a major factor that influences not only the response to antineoplastic therapies but also the potential for malignant progression and metastasis. We review our medicinal electronomics bricolage design of hypoxia-targeting drugs, antiangiogenic hypoxic cell radiosensitizers, sugar-hybrid hypoxic cell radiosensitizers, and hypoxia-targeting 10B delivery agents, in which we design drug candidates based on their electronic structures obtained by molecular orbital calculations, not based solely on pharmacophore development. These drugs include an antiangiogenic hypoxic cell radiosensitizer TX-2036, a sugar-hybrid hypoxic cell radiosensitizer TX-2244, new hypoxia-targeting indoleamine 2,3-dioxygenase (IDO) inhibitors, and a hypoxia-targeting BNCT agent, BSH (sodium borocaptate-10B)-hypoxic cytotoxin tirapazamine (TPZ) hybrid drug TX-2100. We then discuss the concept of boron tracedrugs as a new drug class having broad potential in many areas.

  2. Changing an automated drug inventory control system to a data base design.

    Science.gov (United States)

    Bradish, R A

    1982-09-01

    A pharmacy department's change from indexed sequential access files to a data base management system (DBMS) for purposes of automated inventory control is described. The DBMS has three main functional areas: (1) inventory ordering and accountability, (2) charging of interdepartmental and intradepartmental orders, and (3) data manipulation with report design for management control. There are seven files directly related to the inventory ordering and accountability area. Each record can be accessed directly or through another file. Information on the quantity of a drug on hand, drug(s) supplied by a specific vendor, status of a purchase order, or calculation of an estimated order quantity can be retrieved quickly. In the drug master file, two records contain a reorder point and safety-stock level that are determined by searching the entries in the order history file and vendor master file. The intradepartmental and interdepartmental orders section contains five files assigned to record and store information on drug distribution. All items removed from the stockroom and distributed are recorded, and reports can be generated for itemized bills, total cost by area, and as formatted files for the accounts payable department. The design, development, and implementation of the DBMS took approximately a year using a part-time pharmacist and minimal outside help, while the previous system required constant expensive help of a programmer/analyst. The DBMS has given the pharmacy department a flexible inventory management system with increased drug control, decreased operating expenses, increased use of department personnel, and the ability to develop and enhance other systems.

  3. Identification of designer drug 2C-E (4-ethyl-2, 5-dimethoxy-phenethylamine) in urine following a drug overdose.

    Science.gov (United States)

    Van Vrancken, Michael J; Benavides, Raul; Wians, Frank H

    2013-01-01

    In recent years, access to information regarding acquisition and synthesis of newer designer drugs has been at an all-time high due largely to the Internet. As these drugs have become more prevalent, laboratory techniques have been developed and refined to identify and screen for this burgeoning population of drugs. This provides a unique opportunity for learning about many of these methods. Laboratory testing techniques and instrumentation are obscure to many health care professionals, yet their results are crucial. Here, we present a case of an overdose of an uncommon designer drug (2C-E) and discuss the basics of liquid chromatography and mass spectrometry, two important techniques used in isolating and identifying the drug. Although often overlooked and taken for granted, these techniques can play a pivotal role in the diagnosis and subsequent management of select patients.

  4. Outbreak of hepatitis C virus infection associated with narcotics diversion by an hepatitis C virus-infected surgical technician.

    Science.gov (United States)

    Warner, Amy E; Schaefer, Melissa K; Patel, Priti R; Drobeniuc, Jan; Xia, Guoliang; Lin, Yulin; Khudyakov, Yury; Vonderwahl, Candace W; Miller, Lisa; Thompson, Nicola D

    2015-01-01

    Drug diversion by health care personnel poses a risk for serious patient harm. Public health identified 2 patients diagnosed with acute hepatitis C virus (HCV) infection who shared a common link with a hospital. Further investigation implicated a drug-diverting, HCV-infected surgical technician who was subsequently employed at an ambulatory surgical center. Patients at the 2 facilities were offered testing for HCV infection if they were potentially exposed. Serum from the surgical technician and patients testing positive for HCV but without evidence of infection before their surgical procedure was further tested to determine HCV genotype and quasi-species sequences. Parenteral medication handling practices at the 2 facilities were evaluated. The 2 facilities notified 5970 patients of their possible exposure to HCV, 88% of whom were tested and had results reported to the state public health departments. Eighteen patients had HCV highly related to the surgical technician's virus. The surgical technician gained unauthorized access to fentanyl owing to limitations in procedures for securing controlled substances. Public health surveillance identified an outbreak of HCV infection due to an infected health care provider engaged in diversion of injectable narcotics. The investigation highlights the value of public health surveillance in identifying HCV outbreaks and uncovering a method of drug diversion and its impacts on patients. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  5. Outbreak of hepatitis C virus infection associated with narcotics diversion by an hepatitis C virus–infected surgical technician

    Science.gov (United States)

    Warner, Amy E.; Schaefer, Melissa K.; Patel, Priti R.; Drobeniuc, Jan; Xia, Guoliang; Lin, Yulin; Khudyakov, Yury; Vonderwahl, Candace W.; Miller, Lisa; Thompson, Nicola D.

    2015-01-01

    Background Drug diversion by health care personnel poses a risk for serious patient harm. Public health identified 2 patients diagnosed with acute hepatitis C virus (HCV) infection who shared a common link with a hospital. Further investigation implicated a drug-diverting, HCV-infected surgical technician who was subsequently employed at an ambulatory surgical center. Methods Patients at the 2 facilities were offered testing for HCV infection if they were potentially exposed. Serum from the surgical technician and patients testing positive for HCV but without evidence of infection before their surgical procedure was further tested to determine HCV genotype and quasi-species sequences. Parenteral medication handling practices at the 2 facilities were evaluated. Results The 2 facilities notified 5970 patients of their possible exposure to HCV, 88% of whom were tested and had results reported to the state public health departments. Eighteen patients had HCV highly related to the surgical technician’s virus. The surgical technician gained unauthorized access to fentanyl owing to limitations in procedures for securing controlled substances. Conclusions Public health surveillance identified an outbreak of HCV infection due to an infected health care provider engaged in diversion of injectable narcotics. The investigation highlights the value of public health surveillance in identifying HCV outbreaks and uncovering a method of drug diversion and its impacts on patients. PMID:25442395

  6. Resolution V fractional factorial Design for Screening of factors affecting weakly basic drugs liposomal systems.

    Science.gov (United States)

    El-Helaly, Sara Nageeb; Habib, Basant A; Abd El-Rahman, Mohamed K

    2018-04-21

    This study aims to investigate factors affecting weakly basic drugs liposomal systems. Resolution V fractional factorial design (2 V 5-1 ) is used as an example of screening designs that would better be used as a wise step before proceeding with detailed factors effects or optimization studies. Five factors probable to affect liposomal systems of weakly basic drugs were investigated using Amisulpride as a model drug. Factors studied were; A: Preparation technique B: Phosphatidyl choline (PhC) amount (mg) C: Cholesterol: PhC molar ratio, D: Hydration volume (ml) and E: Sonication type. Levels investigated were; Ammonium sulphate-pH gradient technique or Transmembrane zinc chelation-pH gradient technique, 200 or 400 mg, 0 or 0.5, 10 or 20 ml and bath or probe sonication for A, B, C, D and E respectively. Responses measured were Particle size (PS) (nm), Zeta potential (ZP) (mV) and Entrapment efficiency percent (EE%). Ion selective electrode was used as a novel method for measuring unentrapped drug concentration and calculating entrapment efficiency without the need for liposomal separation. Factors mainly affecting the studied responses were Cholesterol: PhC ratio and hydration volume for PS, preparation technique for ZP and preparation technique and hydration volume for EE%. The applied 2 V 5-1 design enabled the use of only 16 trial combinations for screening the influence of five factors on weakly basic drugs liposomal systems. This clarifies the value of the use of screening experiments before extensive investigation of certain factors in detailed optimization studies. Copyright © 2017. Published by Elsevier B.V.

  7. 77 FR 9946 - Draft Guidance for Industry on Drug Interaction Studies-Study Design, Data Analysis, Implications...

    Science.gov (United States)

    2012-02-21

    ... industry entitled ``Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and... data analysis in the context of identifying potential drug interactions. The guidance also addresses... Studies--Study Design, Data Analysis, and Implications for Dosing and Labeling.'' Comments were received...

  8. 75 FR 8968 - Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0090] Draft Guidance for Industry on Adaptive Design Clinical Trials for Drugs and Biologics; Availability... familiar and less familiar approaches. As more experience is obtained with the less familiar designs...

  9. Design of a RESTful web information system for drug prescription and administration.

    Science.gov (United States)

    Bianchi, Lorenzo; Paganelli, Federica; Pettenati, Maria Chiara; Turchi, Stefano; Ciofi, Lucia; Iadanza, Ernesto; Giuli, Dino

    2014-05-01

    Drug prescription and administration processes strongly impact on the occurrence of risks in medical settings for they can be sources of adverse drug events (ADEs). A properly engineered use of information and communication technologies has proven to be a promising approach to reduce these risks. In this study, we propose PHARMA, a web information system which supports healthcare staff in the secure cooperative execution of drug prescription, transcription and registration tasks. PHARMA allows the easy sharing and management of documents containing drug-related information (i.e., drug prescriptions, medical reports, screening), which is often inconsistent and scattered across different information systems and heterogeneous organization domains (e.g., departments, other hospital facilities). PHARMA enables users to access such information in a consistent and secure way, through the adoption of REST and web-oriented design paradigms and protocols. We describe the implementation of the PHARMA prototype, and we discuss the results of the usability evaluation that we carried out with the staff of a hospital in Florence, Italy.

  10. Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies

    Directory of Open Access Journals (Sweden)

    Komal Parmar

    2015-10-01

    Full Text Available CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS containing Capryol-90 as oil phase for the delivery of Embelin, a poorly water soluble herbal active ingredient. Box-Behnken experimental design was employed to optimise the formulation variables, X1 (amount of oil; Capryol 90, X2 (amount of surfactant; Acrysol EL 135 and X3 (amount of co-surfactant; PEG 400. Systems were appraised for visual characteristics for self emulsifying time, globule size and drug release. Optimised liquid formulations were formulated into free flowing granules (S-SNEDDS by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into tablet. In vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the drug. FT-IR data revealed no physicochemical interaction between drug and excipients. Solid state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution studies. TEM analysis exhibited spherical globules. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical properties. Thus, the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient, Embelin.

  11. The solubility-permeability interplay and oral drug formulation design: Two heads are better than one.

    Science.gov (United States)

    Dahan, Arik; Beig, Avital; Lindley, David; Miller, Jonathan M

    2016-06-01

    Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect on the drug's apparent permeability has been largely overlooked. The mathematical equation to describe the membrane permeability of a drug comprises the membrane/aqueous partition coefficient, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggesting that the solubility and the permeability are closely related, exhibit a certain interplay between them, and treating the one irrespectively of the other may be insufficient. In this article, an overview of this solubility-permeability interplay is provided, and the available data is analyzed in the context of the effort to maximize the overall drug exposure. Overall, depending on the type of solubility-permeability interplay, the permeability may decrease, remain unchanged, and even increase, in a way that may critically affect the formulation capability to improve the overall absorption. Therefore, an intelligent design of solubility-enabling formulation needs to consider both the solubility afforded by the formulation and the permeability in the new luminal environment resulting from the formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. [The use of saliva for exposure assessments on designer drugs among adolescents].

    Science.gov (United States)

    Napierała, Marta; Tezyk, Artur; Piznal, Małgorzata; Bogusiewicz, Joanna; Florek, Ewa

    2015-01-01

    Drug use is one of the fundamental problems of the contemporary world. Due to the debilitating effects on physical and mental health and the possibility of impaired social functions, it is extremely important to assess exposure to psychoactive substances among high-risk groups. Taking into account characteristics of adolescence, one of them includes young people. To assess the exposure of young people to drugs, survey research is the most commonly use. To establish reliability of the information indicated by the students, toxicological studies could be a good manner. High-performance liquid chromatography coupled with mass spectrometry (LC-MS) is currently one of the most common techniques use for the detection and determination of psychoactive substances in biological material. In practice, an important issue in toxicological studies is the selection of a suitable biological material. Taking into account economic considerations and the method of sampling, the saliva is an increasingly used alternative material. The aim of this study was to assess the exposure of junior high school students on psychoactive substances--designer drugs, through the analysis of surveys and qualitative analysis of saliva taken from teenagers. It has been shown that surveys are a relatively quick and easy form of assessing the exposure of young people to psychoactive substances, but require verification through toxicological analysis of biological material for the presence of psychoactive substances for their reliability. Poznan secondary school students experimented with designer drugs at a similar level as respondents of nationwide survey from 2013.

  13. The Food and Drug Administration and Drug Legalization: A Brief Model of Regulation

    OpenAIRE

    Kalam, Murad

    2002-01-01

    This paper offers a brief model of FDA regulation of currently illegal narcotics in the United States. Given that nearly three out of four Americans believe that the drug war has failed, recent calls from prominent liberal and conservative thinkers to legalize drugs, and state “compassionate use†ballot initiatives, future drug legalization is at least conceivable in the United States. Yet, how would the FDA regulate NLD’s under its current st...

  14. Design of inhibitors of thymidylate kinase from Variola virus as new selective drugs against smallpox.

    Science.gov (United States)

    Guimarães, Ana P; de Souza, Felipe R; Oliveira, Aline A; Gonçalves, Arlan S; de Alencastro, Ricardo B; Ramalho, Teodorico C; França, Tanos C C

    2015-02-16

    Recently we constructed a homology model of the enzyme thymidylate kinase from Variola virus (VarTMPK) and proposed it as a new target to the drug design against smallpox. In the present work, we used the antivirals cidofovir and acyclovir as reference compounds to choose eleven compounds as leads to the drug design of inhibitors for VarTMPK. Docking and molecular dynamics (MD) studies of the interactions of these compounds inside VarTMPK and human TMPK (HssTMPK) suggest that they compete for the binding region of the substrate and were used to propose the structures of ten new inhibitors for VarTMPK. Further docking and MD simulations of these compounds, inside VarTMPK and HssTMPK, suggest that nine among ten are potential selective inhibitors of VarTMPK. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Structure-based drug design for G protein-coupled receptors.

    Science.gov (United States)

    Congreve, Miles; Dias, João M; Marshall, Fiona H

    2014-01-01

    Our understanding of the structural biology of G protein-coupled receptors has undergone a transformation over the past 5 years. New protein-ligand complexes are described almost monthly in high profile journals. Appreciation of how small molecules and natural ligands bind to their receptors has the potential to impact enormously how medicinal chemists approach this major class of receptor targets. An outline of the key topics in this field and some recent examples of structure- and fragment-based drug design are described. A table is presented with example views of each G protein-coupled receptor for which there is a published X-ray structure, including interactions with small molecule antagonists, partial and full agonists. The possible implications of these new data for drug design are discussed. © 2014 Elsevier B.V. All rights reserved.

  16. The Semiempirical Quantum Mechanical Scoring Function for In Silico Drug Design

    Czech Academy of Sciences Publication Activity Database

    Lepšík, Martin; Řezáč, Jan; Kolář, Michal; Pecina, Adam; Hobza, Pavel; Fanfrlík, Jindřich

    2013-01-01

    Roč. 78, č. 9 (2013), s. 921-931 ISSN 2192-6506 R&D Projects: GA ČR GBP208/12/G016 Grant - others:Operational Program Research and Development for Innovations(XE) CZ 1.05/2.1.00/03/0058 Institutional support: RVO:61388963 Keywords : computational chemistry * drug design * noncovalent interactions * quantum chemistry * semiempirical calculations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.242, year: 2013

  17. NMR screening in fragment-based drug design: a practical guide.

    Science.gov (United States)

    Kim, Hai-Young; Wyss, Daniel F

    2015-01-01

    Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.

  18. Drug design based on x-ray diffraction and steered molecular dynamics

    Czech Academy of Sciences Publication Activity Database

    Hašek, Jindřich; Skálová, Tereza; Dohnálek, Jan; Dušková, Jarmila; Petroková, Hana; Vondráčková, Eva; Zimmermann, K.

    2005-01-01

    Roč. 12, č. 3 (2005), s. 208-210 ISSN 1211-5894. [VUFB Conference on Modern Methods in Synthesis and Analysis of Active Pharmaceutical Substances /5./. Praha, 23.11.2005-24.11.2005] R&D Projects: GA AV ČR KJB4050312 Institutional research plan: CEZ:AV0Z40500505 Keywords : drug design * X-ray diffraction * steered molecular dynamics Subject RIV: CF - Physical ; Theoretical Chemistry

  19. [Designer drugs and caffeine - characteristics of psychoactive substances and their impact on the organism].

    Science.gov (United States)

    Wierzejska, Regina

    2014-01-01

    For many teenagers the time of growing up is a period of trying prohibited substances. Nowadays apart from alcohol and tobacco new designed, psychoactive substances known as "smart drugs" or "legal highs" are available. Intensive development of their market is taking place in the last few years which is difficult to overcome by regulations only. Toxicological tests used now are not able to detect the presence of many such substances in the body. Designer drugs cause the interest of young people even from small towns and many times taking them give effects requiring medical help. Caffeine is also a psychoactive substance but depending on the dose it can have positive or detrimental effect. Recently there are more and more products with caffeine, especially drinks and dietary supplements, what can cause the increase of consumption of caffeine. Children are particularly exposed to the adverse effect of high consumption of caffeine because of their small body weight and development of the central nervous system. This article presents actual data about the market of designer drugs, frequency of using them, consumption of caffeine by children and teenagers and about the impact of these substances on the organism.

  20. Protein folding and non-conventional drug design: a primer for nuclear structure physicists

    International Nuclear Information System (INIS)

    Broglia, R.A.; Tiana, G.; Provasi, D.

    2004-01-01

    Some of the paradigms emerging from the study of the phenomena of phase transitions in finite many-body systems, like e.g. the atomic nucleus can be used at profit to solve the protein folding problem within the framework of simple (although not oversimplified) models. From this solution a paradigm emerges for the design of non-conventional drugs, which inhibit enzymatic action without inducing resistance (mutations). The application of these concepts to the design of an inhibitor to the HIV-protease central in the life cycle of the HIV virus is discussed

  1. Quality by design case study: an integrated multivariate approach to drug product and process development.

    Science.gov (United States)

    Huang, Jun; Kaul, Goldi; Cai, Chunsheng; Chatlapalli, Ramarao; Hernandez-Abad, Pedro; Ghosh, Krishnendu; Nagi, Arwinder

    2009-12-01

    To facilitate an in-depth process understanding, and offer opportunities for developing control strategies to ensure product quality, a combination of experimental design, optimization and multivariate techniques was integrated into the process development of a drug product. A process DOE was used to evaluate effects of the design factors on manufacturability and final product CQAs, and establish design space to ensure desired CQAs. Two types of analyses were performed to extract maximal information, DOE effect & response surface analysis and multivariate analysis (PCA and PLS). The DOE effect analysis was used to evaluate the interactions and effects of three design factors (water amount, wet massing time and lubrication time), on response variables (blend flow, compressibility and tablet dissolution). The design space was established by the combined use of DOE, optimization and multivariate analysis to ensure desired CQAs. Multivariate analysis of all variables from the DOE batches was conducted to study relationships between the variables and to evaluate the impact of material attributes/process parameters on manufacturability and final product CQAs. The integrated multivariate approach exemplifies application of QbD principles and tools to drug product and process development.

  2. Media milling process optimization for manufacture of drug nanoparticles using design of experiments (DOE).

    Science.gov (United States)

    Nekkanti, Vijaykumar; Marwah, Ashwani; Pillai, Raviraj

    2015-01-01

    Design of experiments (DOE), a component of Quality by Design (QbD), is systematic and simultaneous evaluation of process variables to develop a product with predetermined quality attributes. This article presents a case study to understand the effects of process variables in a bead milling process used for manufacture of drug nanoparticles. Experiments were designed and results were computed according to a 3-factor, 3-level face-centered central composite design (CCD). The factors investigated were motor speed, pump speed and bead volume. Responses analyzed for evaluating these effects and interactions were milling time, particle size and process yield. Process validation batches were executed using the optimum process conditions obtained from software Design-Expert® to evaluate both the repeatability and reproducibility of bead milling technique. Milling time was optimized to process variables by applying DOE resulted in considerable decrease in milling time to achieve the desired particle size. The study indicates the applicability of DOE approach to optimize critical process parameters in the manufacture of drug nanoparticles.

  3. ADMINISTRATIVE AND ORGANIZATIONAL ASPECTS OF FUNCTIONING OF THE SYSTEM OF AVAILABILITY NARCOTIC AND PSYCHOTROPIC MEDICINAL PREPARATIONS FOR PATIENTS WHO NEED THEM

    Directory of Open Access Journals (Sweden)

    I. A. Kaminskaya

    2016-01-01

    Full Text Available Narcotic drugs and psychotropic substances still remain indispensable in medicine. One of the top priorities of health care is to ensure the required availability of this group of drugs. The development of an effective system which can ensure crucially important availability of narcotic and psychotropic agents to people who need them for medical purposes must rely on the identification and analysis of the nature and specificity of the problems related to them as well as the ways of solving these problems. ThePurpose of the Study was to explore the constituents of the system ensuring medicinal availability of narcotic and psychotropic agents and to identify the factors hindering the availability of this group of medicinal agents.Materials and Methods. The study involved the systematic review analysis of the scientific publications and guidance  documents regulating various aspects of activities involving the turnover of controlled drugs, and the results of surveys and interviews in which medical and pharmaceutical professionals were engaged. The study employed the methods of content analysis, logical and functional analysis, etc.Results and Discussion. The system of narcotic and psychotropic drug (NPD availability for patients who need them is currently going through reforms which have been conditioned by low accessibilty of these drugs when used for medical purposes. Those engaged in the drug supply system including medical and pharmaceutical professionals point out that excessive bureaucratization of the system of NPD supply and availability, complexity of documentation and paperwork reporting thedrug flow, costliness of these activities, and strict liability account for low availability of such drugs. To ensure the rights of the citizens to relieve pain due to diseases or medical interventions, a number of changes in the laws and regulations have been made. They have simplified the requirements for NPD

  4. Opportunities and Challenges for Drug Development: Public-Private Partnerships, Adaptive Designs and Big Data.

    Science.gov (United States)

    Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C

    2016-01-01

    Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development.

  5. Designing Decision Support System to Detect Drug Interactions Type 2 Diabetes.

    Science.gov (United States)

    Rasoolimoghadam, Mehdi; Safdari, Reza; Ghazisaeidi, Marjan; Maharanitehrani, MohammadReza; Tahmasebiyan, Shahram

    2015-12-01

    Type II Diabetes is the most common diseases of metabolic disorders and the treatment of oral anti-diabetic drug use takes place But The problem of using multi-drug and interactions at the same time is an issue that has always been a major challenge And diagnosis of drug interactions, particularly in Diabetic patients due to the problem with the disease is very important. The purpose of this studying is, to design a clinical assistant decided to use this approach to determine the type II diabetes drug interactions this makes it easy for those who are active in the field. Study is Developmental that to determine the content of the system a self-made checklist was used. Checklist Validity and reliability has been confirmed by four professors. The Research community to determine the content of the system was country endocrine that are 124 people. The sample size was calculated using Cochran that was 57 people. The Score of checklist was calculated in SPSS version 20 .finally, the checklist was approved by at least 70% points. The system by using Microsoft SQL server 2008 and visual Studio 2012 development environment was designed in C#.net. In the end, In order to evaluate the software to determine the level of satisfaction, usability and ease of use, designed systems sharing with all Medical Informatics students of Tehran University of Medical Sciences. For this purpose a self-made questionnaire was used. Questionnaire Validity has been confirmed by four professors and reliability was assessed by Cronbach method. The results of the survey are showing that the majority of students found out and believed the software is useful and easy to use and generally expressed their satisfaction software. The methodology provides a suitable approach for analysis and modeling of data in the medical field and the performance is good.

  6. Opportunities and challenges for drug development: public-private partnerships, adaptive designs and big data

    Directory of Open Access Journals (Sweden)

    Oktay Yildirim

    2016-12-01

    Full Text Available Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research & Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e. public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development.

  7. Opportunities and Challenges for Drug Development: Public–Private Partnerships, Adaptive Designs and Big Data

    Science.gov (United States)

    Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C.

    2016-01-01

    Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public–private partnerships, adaptive designs and big data. Public–private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development. PMID:27999543

  8. Preoperative intravenous ibuprofen does not influence postoperative narcotic use in patients undergoing elective hernia repair: a randomized, double-blind, placebo controlled prospective trial

    Directory of Open Access Journals (Sweden)

    Sparber LS

    2017-07-01

    Full Text Available Lauren S Sparber,1 Christine SM Lau,1,2 Tanya S Vialet,1 Ronald S Chamberlain1–4 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 4Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Inguinal and umbilical hernia repairs are among the most common surgical procedures performed in the US. Optimal perioperative pain control regimens remain challenging and opioid analgesics are commonly used. Preoperative nonsteroidal anti-inflammatory drug (NSAID administration has been shown to reduce postoperative narcotic requirements. This study sought to evaluate the efficacy of perioperative intravenous (IV ibuprofen on postoperative pain level and narcotic use in patients undergoing open or laparoscopic inguinal and/or umbilical hernia repair.Methods: A single center, randomized, double-blind placebo-controlled trial involving patients ≥18 years undergoing inguinal and/or umbilical hernia repair was performed. Patients were randomized to receive 800 mg of IV ibuprofen or placebo preoperatively. Outcomes assessed included postoperative pain medication required and visual analog scale (VAS pain scores.Results: Forty-eight adult male patients underwent inguinal and/or umbilical hernia repair. Patients receiving IV ibuprofen used more oxycodone/acetaminophen (32% vs 13% and IV hydromorphone (12% vs 8.7%, and fewer combinations of pain medications (44% vs 65.2% in the first two postoperative hours compared to placebo (p=0.556. The IV ibuprofen group had more patients pain free (28% vs 8.7%, p=0.087 and lower VAS scores (3.08±2.14 vs 3.95±1.54, p=0.134 at 2 hours postoperatively, compared to the placebo group, however, this was not statistically significant. Similar pain levels at 1, 3, and 7 days, postoperative and similar use of rescue

  9. Metal complexes in cancer therapy – an update from drug design perspective

    Directory of Open Access Journals (Sweden)

    Ndagi U

    2017-03-01

    Full Text Available Umar Ndagi, Ndumiso Mhlongo, Mahmoud E Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa Abstract: In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field. Recently, however, there has been an upsurge of activities relying on the structural information, aimed at improving and developing other forms of metal-based compounds and nonclassical platinum complexes whose mechanism of action is distinct from known drugs such as cisplatin. In line with this, many more metal-based compounds have been synthesized by redesigning the existing chemical structure through ligand substitution or building the entire new compound with enhanced safety and cytotoxic profile. However, because of increased emphasis on the clinical relevance of metal-based complexes, a few of these drugs are currently on clinical trial and many more are awaiting ethical approval to join the trial. In this review, we seek to give an overview of previous reviews on the cytotoxic effect of metal-based complexes while focusing more on newly designed metal-based complexes and their cytotoxic effect on the cancer cell lines, as well as on new approach to metal-based drug design and molecular target in cancer therapy. We are optimistic that the concept of selective

  10. Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D.

    Science.gov (United States)

    Ke, Zhongcheng; Hou, Xuefeng; Jia, Xiao-Bin

    2016-01-01

    The main purpose of this research was to design a self-nanoemulsifying drug delivery system (SNEDDS) for improving the bioavailability of cyclovirobuxine D as a poorly water-soluble drug. Solubility trials, emulsifying studies, and pseudo-ternary phase diagrams were used to screen the SNEDDS formulations. The optimized drug-loaded SNEDDS was prepared at a mass ratio of 3:24:38:38 for cyclovirobuxine D, oleic acid, Solutol SH15, and propylene glycol, respectively. The optimized formulation was characterized in terms of physicochemical and pharmacokinetic parameters compared with marketed cyclovirobuxine D tablets. The optimized cyclovirobuxine-D-loaded SNEDDS was spontaneously dispersed to form a nanoemulsion with a globule size of 64.80±3.58 nm, which exhibited significant improvement of drug solubility, rapid absorption rate, and enhanced area under the curve, together with increased permeation and decreased efflux. Fortunately, there was a nonsignificant cytotoxic effect toward Caco-2 cells. The relative bioavailability of SNEDDS was 200.22% in comparison with market tablets, in rabbits. SNEDDS could be a potential candidate for an oral dosage form of cyclovirobuxine D with improved bioavailability.

  11. [Benzimidazole and its derivatives--from fungicides to designer drugs. A new occupational and environmental hazards].

    Science.gov (United States)

    Lutz, Piotr

    2012-01-01

    Benzimidazole and benzimidazole derivatives play an important role in controlling various fungal pathogens. The benzimidazoles are also used to treat nematode and trematode infections in humans and animals. It acts by binding to the microtubules and stopping hyphal growth. It also binds to the spindle microtubules and blocks nuclear division. The most popular fungicide is carbendazim. The fungicide is used to control plant diseases in cereals and fruits. Laboratory studies have shown that carbendazim cause infertility and destroy the testicles of laboratory animals. Other benzimidazole derivatives are used as a preservative in paint, textile, papermaking, leather industry, and warehousing practices, as well as a preservative of fruits. Occupational exposure to benzimidazole may occur through inhalation and dermal contact with those compounds at workplaces where benzimidazole is used or produced. Some of the benzimidazoles are common environmental pollutants. They are often found in food and fruit products. Some of the benzimidazoles, like a astemizole or esomeprazole have found applications in diverse therapeutical areas. Despite of the clear advantages afforded by the use of benzimidazole derivatives, they share a danger potential. The most hazardous, however, are new illegally synthesed psychoactive drugs known as designer drugs. Some of them, like nitazene, etonitazene or clonitazene belong to benzimidazole derivatives. Laboratory animal studies revealed that etonitazene produced very similar effects in central nervous system as those observed after morphine administration. Considering etonitazene's properties, it seems reasonable to expected that long-term exposure to other benzimidazole derivatives may result in drug abuse and development of drug dependence.

  12. Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

    Science.gov (United States)

    Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

    2013-01-01

    A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

  13. Does the Drug Facts Label for nonprescription drugs meet its design objectives? A new procedure for assessing label effectiveness

    Directory of Open Access Journals (Sweden)

    Michael P Ryan

    2017-07-01

    Full Text Available We demonstrate an expanded procedure for assessing drug-label comprehension. Innovations include a pretest of drug preconceptions, verbal ability and label attentiveness measures, a label-scanning task, a free-recall test, category-clustering measures, and preconception-change scores. In total, 55 female and 39 male undergraduates read a facsimile Drug Facts Label for aspirin, a Cohesive-Prose Label, or a Scrambled-Prose Label. The Drug Facts Label outperformed the Scrambled-Prose Label, but not the Cohesive-Prose Label, in scanning effectiveness. The Drug Facts Label was no better than the Cohesive-Prose Label or the Scrambled-Prose Label in promoting attentiveness, recall and organization of drug facts, or misconception refutation. Discussion focuses on the need for refutational labels based on a sequence-of-events text schema.

  14. Binding Mode and Induced Fit Predictions for Prospective Computational Drug Design.

    Science.gov (United States)

    Grebner, Christoph; Iegre, Jessica; Ulander, Johan; Edman, Karl; Hogner, Anders; Tyrchan, Christian

    2016-04-25

    Computer-aided drug design plays an important role in medicinal chemistry to obtain insights into molecular mechanisms and to prioritize design strategies. Although significant improvement has been made in structure based design, it still remains a key challenge to accurately model and predict induced fit mechanisms. Most of the current available techniques either do not provide sufficient protein conformational sampling or are too computationally demanding to fit an industrial setting. The current study presents a systematic and exhaustive investigation of predicting binding modes for a range of systems using PELE (Protein Energy Landscape Exploration), an efficient and fast protein-ligand sampling algorithm. The systems analyzed (cytochrome P, kinase, protease, and nuclear hormone receptor) exhibit different complexities of ligand induced fit mechanisms and protein dynamics. The results are compared with results from classical molecular dynamics simulations and (induced fit) docking. This study shows that ligand induced side chain rearrangements and smaller to medium backbone movements are captured well in PELE. Large secondary structure rearrangements, however, remain challenging for all employed techniques. Relevant binding modes (ligand heavy atom RMSD PELE method within a few hours of simulation, positioning PELE as a tool applicable for rapid drug design cycles.

  15. The insults of illicit drug use on male fertility.

    Science.gov (United States)

    Fronczak, Carolyn M; Kim, Edward D; Barqawi, Al B

    2012-01-01

    One-third of infertile couples may have a male factor present. Illicit drug use can be an important cause of male factor infertility and includes use of anabolic-androgenic steroids, marijuana, opioid narcotics, cocaine, and methamphetamines. The use of these illicit drugs is common in the United States, with a yearly prevalence rate for any drug consistently higher in males compared with females. We aim to provide a review of recent literature on the prevalence and effects of illicit drug use on male fertility and to aid health professionals when counseling infertile men whose social history suggests illicit drug use. Anabolic-androgenic steroids, marijuana, cocaine, methamphetamines, and opioid narcotics all negatively impact male fertility, and adverse effects have been reported on the hypothalamic-pituitary-testicular axis, sperm function, and testicular structure. The use of illicit drugs is prevalent in our society and likely adversely impacting the fertility of men who abuse drugs.

  16. Modern drug design: the implication of using artificial neuronal networks and multiple molecular dynamic simulations

    Science.gov (United States)

    Yakovenko, Oleksandr; Jones, Steven J. M.

    2018-01-01

    We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource (https://drugdesigndata.org/). The challenge was focused on the ligands of the farnesoid X receptor (FXR), a highly flexible nuclear receptor of the cholesterol derivative chenodeoxycholic acid. FXR is considered an important therapeutic target for metabolic, inflammatory, bowel and obesity related diseases (Expert Opin Drug Metab Toxicol 4:523-532, 2015), but in the context of this competition it is also interesting due to the significant ligand-induced conformational changes displayed by the protein. To deal with these conformational changes we employed multiple simulations of molecular dynamics (MD). Our MD-based protocols were top-ranked in estimating the free energy of binding of the ligands and FXR protein. Our approach was ranked second in the prediction of the binding poses where we also combined MD with molecular docking and artificial neural networks. Our approach showed mediocre results for high-throughput scoring of interactions.

  17. A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

    Science.gov (United States)

    Yu, Yang; Teerenstra, Steven; Neef, Cees; Burger, David; Maliepaard, Marc

    2016-04-01

    The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. The study was designed as a retrospective reanalysis of existing studies. Nine replicate design bioequivalence studies representing six drug classes - i.e. for alendronate, atorvastatin, cyclosporin, ebastine, exemestane, mycophenolate mofetil, and ropinirole - were retrieved from the Dutch Medicines Regulatory Authority. In most studies, the intrasubject variability in total and peak drug exposure was comparable for the brand-name [in the range 0.01-0.24 for area under the concentration-time curve (AUCt ) and 0.02-0.29 for peak plasma concentration (Cmax ) on a log scale] and generic (0.01-0.23 for AUCt and 0.08-0.33 for Cmax ) drugs, and was comparable with the intrasubject variability upon switching between those drugs (0.01-0.23 for AUCt and 0.06-0.33 for Cmax ). The variance related to subject-by-formulation interaction could be considered negligible (-0.069 to 0.047 for AUCt and -0.091 to 0.02 for Cmax ). In the investigated studies, the variation in total and peak exposure seen when a patient is switched from a brand-name to a generic drug is comparable with that seen following repeated administration of the brand-name drug in the patient. Only the intrasubject variability seems to play a crucial and decisive role in the variation in drug exposure seen; no additional formulation-dependent variation in exposure is observed upon switching. Thus, our data support that, for the medicines that were included in the present investigation, from a clinical pharmacological perspective, the benefit-risk balance of a generic drug is comparable with that of the brand-name drug. © 2015 The British Pharmacological Society.

  18. Efforts of Controlling Money Laundering of Narcotics Money in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Khaled A. ALASMARI

    2014-06-01

    Full Text Available Money laundering is a silent crime. Its goal is to cover up the source of large sums of money that criminals often gather from their criminal activities. This paper will analyze the situation of money laundering in narcotics as it applies in Saudi Arabia. To achieve this end, the paper will first define important terms such as money laundering and narcotics. It will then explain the relationship between money laundering, narcotics trade, and terrorism activities. This background information will form the base for analyzing the various efforts that the Saudi Arabia nation has in place for countering money laundering in narcotics trade. The paper will then explain the challenges facing these efforts, and the future of money laundering in Saudi Arabia. The largest criminal activity associated with money laundering is terrorism financing. The several terror attacks associated with Saudi Arabia’s terror groups like Al-Qaida have made the government realize the importance of curbing money laundering in an effort to counter terrorism. Thus, anti-money laundering strategies are set in place to address all the avenues of money laundering.

  19. Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

    Science.gov (United States)

    Pinsky, C; Dua, A K; LaBella, F S

    1982-07-15

    Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

  20. Effect of narcotics on membrane-bound mitochondrial processes in fish

    DEFF Research Database (Denmark)

    Vergauwen, Lucia; Nørgaard Schmidt, Stine; Michiels, Ellen

    and endoplasmic reticulum membrane are known to closely interact with the cell membrane, we hypothesize that narcotics can be further partitioned into these organelle membranes where they can disrupt essential membrane-bound processes. The electron transport chain (ETC) is an example of a crucial mitochondrial...

  1. 21 CFR 1304.31 - Reports from manufacturers importing narcotic raw material.

    Science.gov (United States)

    2010-04-01

    ... therefrom. (g) All in-process inventories should be expressed in terms of end-products and not precursors... following information shall be submitted for each type of narcotic raw material (quantities are expressed as... opium, crude alkaloids and other derivatives (quantities are expressed as grams of anhydrous base or...

  2. Detection of Stimulants and Narcotics by Liquid Chromatography-Tandem Mass Spectrometry and Gas Chromatography-Mass Spectrometry for Sports Doping Control.

    Science.gov (United States)

    Ahrens, Brian D; Kucherova, Yulia; Butch, Anthony W

    2016-01-01

    Sports drug testing laboratories are required to detect several classes of compounds that are prohibited at all times, which include anabolic agents, peptide hormones, growth factors, beta-2 agonists, hormones and metabolic modulators, and diuretics/masking agents. Other classes of compounds such as stimulants, narcotics, cannabinoids, and glucocorticoids are also prohibited, but only when an athlete is in competition. A single class of compounds can contain a large number of prohibited substances and all of the compounds should be detected by the testing procedure. Since there are almost 70 stimulants on the prohibited list it can be a challenge to develop a single screening method that will optimally detect all the compounds. We describe a combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) testing method for detection of all the stimulants and narcotics on the World Anti-Doping Agency prohibited list. Urine for LC-MS/MS testing does not require sample pretreatment and is a direct dilute and shoot method. Urine samples for the GC-MS method require a liquid-liquid extraction followed by derivatization with trifluoroacetic anhydride.

  3. Narcotic Use and Postoperative Doctor Shopping by Patients with Nephrolithiasis Requiring Operative Intervention: Implications for Patient Safety.

    Science.gov (United States)

    Kappa, Stephen F; Green, Elizabeth A; Miller, Nicole L; Herrell, Stanley D; Mitchell, Christopher R; Mir, Hassan R; Resnick, Matthew J

    2016-09-01

    We sought to determine perioperative patterns of narcotic use and the prevalence of postoperative doctor shopping among patients with nephrolithiasis requiring operative management. We retrospectively reviewed the records of consecutive patients residing in Tennessee who required ureteroscopy with laser lithotripsy for nephrolithiasis at a single institution from January to December 2013. Using the Tennessee CSMD (Controlled Substances Medication Database) patients were categorized by the number of postoperative narcotic providers. Doctor shopping behavior was identified as any patient seeking more than 1 narcotic provider within 3 months of surgery. Demographic and clinical characteristics associated with doctor shopping behavior were identified. During the study period 200 eligible patients underwent ureteroscopy with laser lithotripsy for nephrolithiasis, of whom 48 (24%) were prescribed narcotics by more than 1 provider after surgery. Compared to those receiving narcotics from a single provider, patients with multiple narcotic providers were younger (48.1 vs 54.2 years, p shopping is common among patients with nephrolithiasis who require operative management. Urologists should be aware of available registry data to decrease the likelihood of redundant narcotic prescribing. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Evolutions in fragment-based drug design: the deconstruction–reconstruction approach

    Science.gov (United States)

    Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia

    2014-01-01

    Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697

  5. History and evolution of the pharmacophore concept in computer-aided drug design.

    Science.gov (United States)

    Güner, Osman F

    2002-12-01

    With computer-aided drug design established as an integral part of the lead discovery and optimization process, pharmacophores have become a focal point for conceptualizing and understanding receptor-ligand interactions. In the structure-based design process, pharmacophores can be used to align molecules based on the three-dimensional arrangement of chemical features or to develop predictive models (e.g., 3D-QSAR) that correlate with the experimental activities of a given training set. Pharmacophores can be also used as search queries for retrieving potential leads from structural databases, for designing molecules with specific desired attributes, or as fingerprints for assessing similarity and diversity of molecules. This review article presents a historical perspective on the evolution and use of the pharmacophore concept in the pharmaceutical, biotechnology, and fragrances industry with published examples of how the technology has contributed and advanced the field.

  6. Design and optimization of self-nanoemulsifying drug delivery systems for improved bioavailability of cyclovirobuxine D

    Directory of Open Access Journals (Sweden)

    Ke ZC

    2016-06-01

    Full Text Available Zhongcheng Ke,1–3 Xuefeng Hou,4 Xiao-bin Jia31Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 2Huangshan University, Huangshan, Anhui, 3Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 4Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of ChinaBackground: The main purpose of this research was to design a self-nanoemulsifying drug delivery system (SNEDDS for improving the bioavailability of cyclovirobuxine D as a poorly water-soluble drug.Materials and methods: Solubility trials, emulsifying studies, and pseudo-ternary phase diagrams were used to screen the SNEDDS formulations. The optimized drug-loaded SNEDDS was prepared at a mass ratio of 3:24:38:38 for cyclovirobuxine D, oleic acid, Solutol SH15, and propylene glycol, respectively. The optimized formulation was characterized in terms of physicochemical and pharmacokinetic parameters compared with marketed cyclovirobuxine D tablets.Results: The optimized cyclovirobuxine-D-loaded SNEDDS was spontaneously dispersed to form a nanoemulsion with a globule size of 64.80±3.58 nm, which exhibited significant improvement of drug solubility, rapid absorption rate, and enhanced area under the curve, together with increased permeation and decreased efflux. Fortunately, there was a nonsignificant cytotoxic effect toward Caco-2 cells. The relative bioavailability of SNEDDS was 200.22% in comparison with market tablets, in rabbits.Conclusion: SNEDDS could be a potential candidate for an oral dosage form of cyclovirobuxine D with improved bioavailability.Keywords: self-nanoemulsifying drug delivery, bioavailability, cyclovirobuxine D

  7. Design and Characterization of a Silk-Fibroin-Based Drug Delivery Platform Using Naproxen as a Model Drug

    Directory of Open Access Journals (Sweden)

    Tatyana Dyakonov

    2012-01-01

    Full Text Available The objective of this proof-of-concept study was to develop a platform for controlled drug delivery based on silk fibroin (SF and to explore the feasibility of using SF in oral drug delivery. The SF-containing matrixes were prepared via spray-drying and film casting, and the release profile of the model drug naproxen sodium was evaluated. Attenuated total reflectance Fourier transform infrared spectroscopy (FTIR has been used to observe conformational changes in SF- and drug-containing compositions. SF-based films, spray-dried microparticles, and matrixes loaded with naproxen were prepared. Both FTIR spectra and in vitro dissolution data demonstrated that SF β-sheet conformation regulates the release profile of naproxen. The controlled release characteristics of the SF-containing compositions were evaluated as a function of SF concentration, temperature, and exposure to dehydrating solvents. The results suggest that SF may be an attractive polymer for use in controlled drug delivery systems.

  8. [Characteristics of the development of drug addiction and toxicomania in adolescents].

    Science.gov (United States)

    Lukacher, G Ia; Makshantseva, N V

    1988-01-01

    The study involved 152 adolescents which had abused narcotic and toxic substances once, occasionally or regularly. Males aged 15 to 16 years displayed highest occurrence rate of the abuse. Drug addiction and toxicomania were established in 6% of subjects. Volatile stuff and tranquilizers were most frequent in use. Microsocial adversities were experienced by all the subjects. Besides, an "altered background" is characteristic of drug addicts and toxicomania patients. The fact of narcotic and toxic substances usage as euphorigenic agents deserves due attention of narcologists, pedagogues, sociologists. Biologically conditioned risk factors conducive to drug addiction and toxicomania should be investigated.

  9. Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design.

    Science.gov (United States)

    Neshich, Izabella Agostinho Pena; Nishimura, Leticia; de Moraes, Fabio Rogerio; Salim, Jose Augusto; Villalta-Romero, Fabian; Borro, Luiz; Yano, Inacio Henrique; Mazoni, Ivan; Tasic, Ljubica; Jardine, Jose Gilberto; Neshich, Goran

    2015-01-01

    The term "agrochemicals" is used in its generic form to represent a spectrum of pesticides, such as insecticides, fungicides or bactericides. They contain active components designed for optimized pest management and control, therefore allowing for economically sound and labor efficient agricultural production. A "drug" on the other side is a term that is used for compounds designed for controlling human diseases. Although drugs are subjected to much more severe testing and regulation procedures before reaching the market, they might contain exactly the same active ingredient as certain agrochemicals, what is the case described in present work, showing how a small chemical compound might be used to control pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates citrus plantations, as well as for control of, for example, meningitis in humans. It is also clear that so far the production of new agrochemicals is not benefiting as much from the in silico new chemical compound identification/discovery as pharmaceutical production. Rational drug design crucially depends on detailed knowledge of structural information about the receptor (target protein) and the ligand (drug/agrochemical). The interaction between the two molecules is the subject of analysis that aims to understand relationship between structure and function, mainly deciphering some fundamental elements of the nanoenvironment where the interaction occurs. In this work we will emphasize the role of understanding nanoenvironmental factors that guide recognition and interaction of target protein and its function modifier, an agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for two selected and specific cases we have approached in order to offer a technological solution for some very important problems that needs special attention in agriculture: elimination of pathogenicity of a bacterium which is attacking citrus plants and formulation of a new fungicide. Finally

  10. Application of mixture experimental design in formulation and characterization of solid self-nanoemulsifying drug delivery systems containing carbamazepine

    OpenAIRE

    Krstić Marko Z.; Ibrić Svetlana R.

    2016-01-01

    One of the problems with orally used drugs is their poor solubility, which can be overcame by creating solid self-nanoemulsifying drug delivery systems (SNEDDS). Aim is choosing appropriate SNEDDS using mixture design and adsorption of SNEDDS on a solid carrier to improve the dissolution rate of carbamazepine. Self-emulsifying drug delivery systems (SEDDS) consisting of oil phase (caprilic-capric triglycerides), a surfactant (Polisorbat 80 and Labrasol® (1:...

  11. An Experimental Comparison of a Co-Design Visualizing Personal Drug Information and Patient Information Leaflets: Usability Aspects.

    Science.gov (United States)

    Khodambashi, Soudabeh; Haugland, Dagrun; Ellingsberg, Anette; Kottum, Hanne; Sund, Janne Kutschera; Nytrø, Øystein

    2017-01-01

    Providing patients with specific information about their own drugs can reduce unintentional misuse and improve compliance. Searching for information is time-consuming when information is not personalized and is written using medical vocabulary that is difficult for patients to understand. In this study we explored patient information needs regarding visualizing of drug information and interrelationships by conducting a total of four co-design workshops with patients, other users and pharmacists. We developed a prototype and drug ontology to support reasoning about drug interactions. We evaluated individual performance in finding information, understanding the drug interactions, and learning from the provided information in the prototype compared to using patient information leaflets (PILs). We concluded that interactive visualization of drug information helps individuals find information about drugs, their side effects and interactions more quickly and correctly compared to using PILs. Our study is limited to co-morbid patients with transient ischaemic attack with several chronic diseases.

  12. Structure-Based Design of Novel HIV-1 Protease Inhibitors to Combat Drug Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh,A.; Sridhar, P.; Leshchenko, S.; Hussain, A.; Li, J.; Kovalevsky, A.; Walters, D.; Wedelind, J.; Grum-Tokars, V.; et al.

    2006-01-01

    Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 Angstroms resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.

  13. Concept of combinatorial de novo design of drug-like molecules by particle swarm optimization.

    Science.gov (United States)

    Hartenfeller, Markus; Proschak, Ewgenij; Schüller, Andreas; Schneider, Gisbert

    2008-07-01

    We present a fast stochastic optimization algorithm for fragment-based molecular de novo design (COLIBREE, Combinatorial Library Breeding). The search strategy is based on a discrete version of particle swarm optimization. Molecules are represented by a scaffold, which remains constant during optimization, and variable linkers and side chains. Different linkers represent virtual chemical reactions. Side-chain building blocks were obtained from pseudo-retrosynthetic dissection of large compound databases. Here, ligand-based design was performed using chemically advanced template search (CATS) topological pharmacophore similarity to reference ligands as fitness function. A weighting scheme was included for particle swarm optimization-based molecular design, which permits the use of many reference ligands and allows for positive and negative design to be performed simultaneously. In a case study, the approach was applied to the de novo design of potential peroxisome proliferator-activated receptor subtype-selective agonists. The results demonstrate the ability of the technique to cope with large combinatorial chemistry spaces and its applicability to focused library design. The technique was able to perform exploitation of a known scheme and at the same time explorative search for novel ligands within the framework of a given molecular core structure. It thereby represents a practical solution for compound screening in the early hit and lead finding phase of a drug discovery project.

  14. CRITICAL ASSESSMENT OF CONTRIBUTION FROM INDIAN PUBLICATIONS: THE ROLE OF IN SILICO DESIGNING METHODS LEADING TO DRUGS OR DRUG-LIKE COMPOUNDS USING TEXT BASED MINING AND ASSOCIATION

    Directory of Open Access Journals (Sweden)

    Pawan Kumar

    2017-09-01

    Full Text Available Over the several decades, India is constantly challenged by communicable and non-communicable diseases which are originated either by poor lifestyle or by environmental factors. The pools of diseases are constantly posing serious threats to mankind especially among the poverty-stricken families. Scientific communities across the globe are working continuously to design drug molecules to overcome the burden of these life threaten diseases. In last three decades, many computational algorithms and tools have been developed to identify potential drug targets and their inhibitors. It is believed that computational techniques have reduced the time and money required to develop an inhibitor into drug. However, applicability and deliverability of these in silico techniques in rational drug designing are not fully evaluated. In the present study, PubMed/Medline extracted data driven analysis has been performed to highlight the influence and progress of the theoretical methods in the field of drug discovery across India and compared with the world. Drug discovery related keyword dictionary has been built and utilized to select only drug discovery related PubMed abstract. A second keyword set (related to bioinformatics tools is used for normalized pointwise mutual information (PMI based association analysis. Observations show that drug discovery has been an interdisciplinary research and used many tools starting with QSAR, docking, pharmacophore, Molecular Simulations etc. The publications contributed from India (2% are similar as compared to the contribution in total world publications, suggesting large scope in future. Data coverage as represented since 1990-2015 in PubMed as indicated by number of publications associated with drug discovery is almost same in world and India (~75%. Emerging institutes/Universities are contributing since last 10 years as observed from Indian publication list. However, this method has many limitations as discussed.

  15. Anti-tuberculosis drug combination for controlled oral delivery using 3D printed compartmental dosage forms: From drug product design to in vivo testing

    DEFF Research Database (Denmark)

    Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano

    2017-01-01

    for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion...... (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution...

  16. Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.

    Science.gov (United States)

    Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun

    2011-12-01

    In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Missing Fragments: Detecting Cooperative Binding in Fragment-Based Drug Design

    Science.gov (United States)

    2012-01-01

    The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads. PMID:24900472

  18. Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

    Science.gov (United States)

    Friedmann, Peter D.; Katz, Elizabeth C.; Rhodes, Anne G.; Taxman, Faye S.; O'Connell, Daniel J.; Frisman, Linda K.; Burdon, William M.; Fletcher, Bennett W.; Litt, Mark D.; Clarke, Jennifer; Martin, Steven S.

    2008-01-01

    This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment…

  19. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Guarino, Vincenzo, E-mail: vguarino@unina.it; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi [Institute for Polymers, Composites and Biomaterials, Department of Chemical Sciences & Materials Technology, National Research Council of Italy, V.le Kennedy 54, Naples (Italy)

    2015-12-17

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial’s manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell–biomaterial and cell– cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

  20. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    International Nuclear Information System (INIS)

    Guarino, Vincenzo; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi

    2015-01-01

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial’s manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell–biomaterial and cell– cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues

  1. Electro fluido dynamic techniques to design instructive biomaterials for tissue engineering and drug delivery

    Science.gov (United States)

    Guarino, Vincenzo; Altobelli, Rosaria; Cirillo, Valentina; Ambrosio, Luigi

    2015-12-01

    A large variety of processes and tools is continuously investigated to discover new solutions to design instructive materials with controlled chemical, physical and biological properties for tissue engineering and drug delivery. Among them, electro fluido dynamic techniques (EFDTs) are emerging as an interesting strategy, based on highly flexible and low-cost processes, to revisit old biomaterial's manufacturing approach by utilizing electrostatic forces as the driving force for the fabrication of 3D architectures with controlled physical and chemical functionalities to guide in vitro and in vivo cell activities. By a rational selection of polymer solution properties and process conditions, EFDTs allow to produce fibres and/or particles at micro and/or nanometric size scale which may be variously assembled by tailored experimental setups, thus giving the chance to generate a plethora of different 3D devices able to incorporate biopolymers (i.e., proteins, polysaccharides) or active molecules (e.g., drugs) for different applications. Here, we focus on the optimization of basic EFDTs - namely electrospinning, electrospraying and electrodynamic atomization - to develop active platforms (i.e., monocomponent, protein and drug loaded scaffolds and µ-scaffolds) made of synthetic (PCL, PLGA) or natural (chitosan, alginate) polymers. In particular, we investigate how to set materials and process parameters to impart specific morphological, biochemical or physical cues to trigger all the fundamental cell-biomaterial and cell- cell cross-talking elicited during regenerative processes, in order to reproduce the complex microenvironment of native or pathological tissues.

  2. Re-sensitizing drug-resistant bacteria to antibiotics by designing Antisense Therapeutics

    Science.gov (United States)

    Courtney, Colleen; Chatterjee, Anushree

    2014-03-01

    ``Super-bugs'' or ``multi-drug resistant organisms'' are a serious international health problem, with devastating consequences to patient health care. The Center for Disease Control has identified antibiotic resistance as one of the world's most pressing public health problems as a significant fraction of bacterial infections contracted are drug resistant. Typically, antibiotic resistance is encoded by ``resistance-genes'' which express proteins that carryout the resistance causing functions inside the bacterium. We present a RNA based therapeutic strategy for designing antimicrobials capable of re-sensitizing resistant bacteria to antibiotics by targeting labile regions of messenger RNAs encoding for resistance-causing proteins. We perform in silico RNA secondary structure modeling to identify labile target regions in an mRNA of interest. A synthetic biology approach is then used to administer antisense nucleic acids to our model system of ampicillin resistant Escherichia coli. Our results show a prolonged lag phase and decrease in viability of drug-resistant E. colitreated with antisense molecules. The antisense strategy can be applied to alter expression of other genes in antibiotic resistance pathways or other pathways of interest.

  3. Progress in bipolar disorder drug design toward the development of novel therapeutic targets: a clinician's perspective.

    Science.gov (United States)

    Fornaro, Michele; Kardash, Lubna; Novello, Stefano; Fusco, Andrea; Anastasia, Annalisa; De Berardis, Domenico; Perna, Giampaolo; Carta, Mauro Giovanni

    2018-03-01

    Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear. Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD. Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

  4. From chemical graphs in computer-aided drug design to general Markov-Galvez indices of drug-target, proteome, drug-parasitic disease, technological, and social-legal networks.

    Science.gov (United States)

    Riera-Fernández, Pablo; Munteanu, Cristian R; Dorado, Julian; Martin-Romalde, Raquel; Duardo-Sanchez, Aliuska; González-Diaz, Humberto

    2011-12-01

    Complex Networks are useful in solving problems in drug research and industry, developing mathematical representations of different systems. These systems move in a wide range from relatively simple graph representations of drug molecular structures to large systems. We can cite for instance, drug-target protein interaction networks, drug policy legislation networks, or drug treatment in large geographical disease spreading networks. In any case, all these networks have essentially the same components: nodes (atoms, drugs, proteins, microorganisms and/or parasites, geographical areas, drug policy legislations, etc.) and edges (chemical bonds, drug-target interactions, drug-parasite treatment, drug use, etc.). Consequently, we can use the same type of numeric parameters called Topological Indices (TIs) to describe the connectivity patterns in all these kinds of Complex Networks despite the nature of the object they represent. The main reason for this success of TIs is the high flexibility of this theory to solve in a fast but rigorous way many apparently unrelated problems in all these disciplines. Another important reason for the success of TIs is that using these parameters as inputs we can find Quantitative Structure-Property Relationships (QSPR) models for different kind of problems in Computer-Aided Drug Design (CADD). Taking into account all the above-mentioned aspects, the present work is aimed at offering a common background to all the manuscripts presented in this special issue. In so doing, we make a review of the most common types of complex networks involving drugs or their targets. In addition, we review both classic TIs that have been used to describe the molecular structure of drugs and/or larger complex networks. Next, we use for the first time a Markov chain model to generalize Galvez TIs to higher order analogues coined here as the Markov-Galvez TIs of order k (MGk). Lastly, we illustrate the calculation of MGk values for different classes of

  5. Design of dual action antibiotics as an approach to search for new promising drugs

    International Nuclear Information System (INIS)

    Tevyashova, A N; Olsufyeva, E N; Preobrazhenskaya, M N

    2015-01-01

    The review is devoted to the latest achievements in the design of dual action antibiotics — heterodimeric (chimeric) structures based on antibacterial agents of different classes (fluoroquinolones, anthracyclines, oxazolidines, macrolides and so on). Covalent binding can make the pharmacokinetic characteristics of these molecules more predictable and improve the penetration of each component into the cell. Consequently, not only does the drug efficacy increase owing to inhibition of two targets but also the resistance to one or both antibiotics can be overcome. The theoretical grounds of elaboration, design principles and methods for the synthesis of dual action antibiotics are considered. The structures are classified according to the type of covalent spacer (cleavable or not) connecting the moieties of two agents. Dual action antibiotics with a spacer that can be cleaved in a living cell are considered as dual action prodrugs. Data on the biological action of heterodimeric compounds are presented and structure–activity relationships are analyzed. The bibliography includes 225 references

  6. Promising Practices in Drug Treatment: Findings from Southeast Asia

    Science.gov (United States)

    Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…

  7. Core-shell designed scaffolds for drug delivery and tissue engineering.

    Science.gov (United States)

    Perez, Roman A; Kim, Hae-Won

    2015-07-01

    Scaffolds that secure and deliver therapeutic ingredients like signaling molecules and stem cells hold great promise for drug delivery and tissue engineering. Employing a core-shell design for scaffolds provides a promising solution. Some unique methods, such as co-concentric nozzle extrusion, microfluidics generation, and chemical confinement reactions, have been successful in producing core-shelled nano/microfibers and nano/microspheres. Signaling molecules and drugs, spatially allocated to the core and/or shell part, can be delivered in a controllable and sequential manner for optimal therapeutic effects. Stem cells can be loaded within the core part on-demand, safely protected from the environments, which ultimately affords ex vivo culture and in vivo tissue engineering. The encapsulated cells experience three-dimensional tissue-mimic microenvironments in which therapeutic molecules are secreted to the surrounding tissues through the semi-permeable shell. Tuning the material properties of the core and shell, changing the geometrical parameters, and shaping them into proper forms significantly influence the release behaviors of biomolecules and the fate of the cells. This topical issue highlights the immense usefulness of core-shell designs for the therapeutic actions of scaffolds in the delivery of signaling molecules and stem cells for tissue regeneration and disease treatment. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Synthetic Cathinone and Cannabinoid Designer Drugs Pose a Major Risk for Public Health

    Directory of Open Access Journals (Sweden)

    Aviv M. Weinstein

    2017-08-01

    Full Text Available As part of an increasing worldwide use of designer drugs, recent use of compounds containing cathinones and synthetic cannabinoids is especially prevalent. Here, we reviewed current literature on the prevalence, epidemiology, bio-behavioral effects, and detection of these compounds. Gender differences and clinical effects will also be examined. Chronic use of synthetic cathinone compounds can have major effects on the central nervous system and can induce acute psychosis, hypomania, paranoid ideation, and delusions, similar to the effects of other better-known amphetamine-type stimulants. Synthetic cannabinoid products have effects that are somewhat similar to those of natural cannabis but more potent and long-lasting than THC. Some of these compounds are potent and dangerous, having been linked to psychosis, mania, and suicidal ideation. Novel compounds are developed rapidly and new screening techniques are needed to detect them as well as a rigorous regulation and legislation reinforcement to prevent their distribution and use. Given the rapid increase in the use of synthetic cathinones and cannabinoid designer drugs, their potential for dependence and abuse, and harmful medical and psychiatric effects, there is a need for research and education in the areas of prevention and treatment.

  9. Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil.

    Science.gov (United States)

    Villar, Ana Maria Sierra; Naveros, Beatriz Clares; Campmany, Ana Cristina Calpena; Trenchs, Monserrat Aróztegui; Rocabert, Coloma Barbé; Bellowa, Lyda Halbaut

    2012-07-15

    Self-nanoemulsifying drug delivery systems of gemfibrozil were developed under Quality by Design approach for improvement of dissolution and oral absorption. Preliminary screening was performed to select proper components combination. Box-Behnken experimental design was employed as statistical tool to optimize the formulation variables, X(1) (Cremophor(®) EL), X(2) (Capmul(®) MCM-C8), and X(3) (lemon essential oil). Systems were assessed for visual characteristics (emulsification efficacy), turbidity, droplet size, polydispersity index and drug release. Different pH media were also assayed for optimization. Following optimization, the values of formulation components (X(1), X(2), and X(3)) were 32.43%, 29.73% and 21.62%, respectively (16.22% of gemfibrozil). Transmission electron microscopy demonstrated spherical droplet morphology. SNEEDS release study was compared to commercial tablets. Optimized SNEDDS formulation of gemfibrozil showed a significant increase in dissolution rate compared to conventional tablets. Both formulations followed Weibull mathematical model release with a significant difference in t(d) parameter in favor of the SNEDDS. Equally amodelistic parameters were calculated being the dissolution efficiency significantly higher for SNEDDS, confirming that the developed SNEDDS formulation was superior to commercial formulation with respect to in vitro dissolution profile. This paper provides an overview of the SNEDDS of the gemfibrozil as a promising alternative to improve oral absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Fragment informatics and computational fragment-based drug design: an overview and update.

    Science.gov (United States)

    Sheng, Chunquan; Zhang, Wannian

    2013-05-01

    Fragment-based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment-based cheminformatics tools, high-throughput fragment docking, and fragment-based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research. © 2012 Wiley Periodicals, Inc.

  11. 3,4-methylenedioxypyrovalerone (MDPV): chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online.

    Science.gov (United States)

    Coppola, M; Mondola, R

    2012-01-05

    The illicit marketplace of substances of abuse continually offers for sale legal alternatives to controlled drugs to a large public. In recent years, a new group of designer drugs, the synthetic cathinones, has emerged as a new trend, particularly among young people. The 3,4-methylenedioxypyrovalerone (MDPV), one of this synthetic compounds, caused an international alert for its cardiovascular and neurological toxicity. This substance, sold as bath salts, has caused many serious intoxications and some deaths in several countries. The aim of this paper is summarise the clinical, pharmacological and toxicological information about this new designer drug. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors.

    Science.gov (United States)

    Furlong, Michael; Seong, Jae Young

    2017-01-01

    Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

  13. Long-term usage of narcotic analgesics by chronic intractable noncancer pain patients in Taiwan from 2003 to 2012

    Directory of Open Access Journals (Sweden)

    I-Chen Cheng

    2016-09-01

    Conclusion: To decrease malaise and addiction in patients with CINCP, Taiwan's physicians need more education on narcotic analgesics, and greater professional cooperation to develop therapeutic guidelines that will improve pain care for patients with CINCP.

  14. Drug Treatment in New York City and Washington, D.C.: Followup Studies.

    Science.gov (United States)

    Burt Associates, Inc., Bethesda, MD.

    This report assesses the experiences of clients who had contact with or received drug abuse treatment from programs of the Addiction Services Agency in New York City and the Narcotics Treatment Administration in Washington, D.C. during the early 1970's. To answer the questions of what happens to former clients once they leave drug treatment…

  15. What Will Happen if . . . A Programmed Instruction Course on Drugs and Their Effects.

    Science.gov (United States)

    Health Services and Mental Health Administration (DHEW), Bethesda, MD.

    Developed by the National Institute of Mental Health, this booklet offers a programed instruction course on drugs and their effects. The purpose of the text is to learn about specific drugs which are currently being used and abused by a large group of people in our society. Narcotics, stimulants, depressants, hallucinogens, and marihuana are…

  16. A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

    Science.gov (United States)

    Poulin, Patrick

    2015-07-01

    fraction in plasma derived from a static in vitro environment might be biased to guide drug design (the old paradigm), and, hence, it is recommended to use a PBPK model to reproduce more accurately the in vivo condition in tissue (the new paradigm). This newly developed approach can be used to predict free drug concentration in diverse tissue compartments for small molecules in toxicology and pharmacology studies, which can be leveraged to optimize the pharmacokinetics drivers of tissue distribution based upon physicochemical and physiological input parameters in an attempt to optimize free drug level in tissue. Overall, this present study provides guidance on the application of plasma and tissue concentration information in PBPK/PD research in preclinical and clinical studies, which is in accordance with the recent literature. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Targeting the dopamine D3 receptor: an overview of drug design strategies.

    Science.gov (United States)

    Cortés, Antoni; Moreno, Estefanía; Rodríguez-Ruiz, Mar; Canela, Enric I; Casadó, Vicent

    2016-07-01

    Dopamine is a neurotransmitter widely distributed in both the periphery and the central nervous system (CNS). Its physiological effects are mediated by five closely related G protein-coupled receptors (GPCRs) that are divided into two major subclasses: the D1-like (D1, D5) and the D2-like (D2, D3, D4) receptors. D3 receptors (D3Rs) have the highest density in the limbic areas of the brain, which are associated with cognitive and emotional functions. These receptors are therefore attractive targets for therapeutic management. This review summarizes the functional and pharmacological characteristics of D3Rs, including the design and clinical relevance of full agonists, partial agonists and antagonists, as well as the capacity of these receptors to form active homodimers, heterodimers or higher order receptor complexes as pharmacological targets in several neurological and neurodegenerative disorders. The high sequence homology between D3R and the D2-type challenges the development of D3R-selective compounds. The design of new D3R-preferential ligands with improved physicochemical properties should provide a better pharmacokinetic/bioavailability profile and lesser toxicity than is found with existing D3R ligands. It is also essential to optimize D3R affinity and, especially, D3R vs. D2-type binding and functional selectivity ratios. Developing allosteric and bitopic ligands should help to improve the D3R selectivity of these drugs. As most evidence points to the ability of GPCRs to form homomers and heteromers, the most promising therapeutic strategy in the future is likely to involve the application of heteromer-selective drugs. These selective ligands would display different affinities for a given receptor depending on the receptor partners within the heteromer. Therefore, designing novel compounds that specifically target and modulate D1R-D3R heteromers would be an interesting approach for the treatment of levodopa (L-DOPA)-induced dyskinesias.

  18. Survey of the Effective Methods of Decreasing Demands of Narcotic Substances from the Viewpoint of Hamadan People

    Directory of Open Access Journals (Sweden)

    A.R. Rahimi

    2007-01-01

    Full Text Available Introduction & Objective: Addiction is a complex problem with different psychological, social and familial aspects, which strongly threaten the health of million people, and collapse the social and personal life. The aim of this study was to determine the effective methods of narcotic substances and decreasing demands from the viewpoint of Hamadan peopleMaterials & Methods: This research was a sectional-descriptive study. The participants consisted of 1456 individuals that were selected by stratified sampling. The data collected through a questionnaire consists of 3 parts; I. the demographic characteristics II. the questions about decreasing the demands and III. the questions related to the methods of narcotic substances campaign.Results: Outcome showed that 60.78% of the participants believe the best method to decrease demands to narcotic substances is the mass media and 51.92% believe to promote the religious believes and 44.5% to change people’s viewpoint about the narcotic substances. 78.85% agreed with using punishments on narcotics devisers and 40.1% agreed with punishment on users.Conclusion: From the viewpoint of Hamedan people mass media and religious believes effect in attitude of people about narcotic substances abuse and also they believed that punishment of users and opinion devisers were being useful.

  19. Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

    Science.gov (United States)

    Perucca, Emilio

    2008-01-01

    Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of

  20. Frequency and structure of stimulant designer drug consumption among suspected drug users in Budapest and South-East Hungary in 2012-2013.

    Science.gov (United States)

    Institóris, László; Árok, Zsófia; Seprenyi, Katalin; Varga, Tibor; Sára-Klausz, Gabriella; Keller, Éva; Tóth, Réka A; Sala, Leonardo; Kereszty, Éva; Róna, Kálmán

    2015-03-01

    Identification of abuse and frequency patterns of stimulant designer drugs (SDDs) provides important information for their risk assessment and legislative control. In the present study urine and/or blood samples of suspected drug users in criminal cases were analysed by GC-MS for 38 SDDs, and for the most frequent illicit and psychoactive licit drugs in Hungary. Between July 2012 and June 2013, 2744 suspected drug users were sampled in Budapest and during 2012 and 2013, 774 persons were sampled in South-East Hungary (Csongrád County - neighbour the Romanian and Serbian borders). In Budapest 71.4% of cases, and in South-East Hungary 61% of cases were positive for at least one substance. Pentedrone was the most frequent SDD in both regions; however, the frequency distribution of the remaining drugs was highly diverse. SDDs were frequently present in combination with other drugs - generally with amphetamine or other stimulants, cannabis and/or benzodiazepines. The quarterly distribution of positive samples indicated remarkable seasonal changes in the frequency and pattern of consumption. Substances placed on the list of illicit drugs (mephedrone, 4-fluoro-amphetamine, MDPV, methylone, 4-MEC) showed a subsequent drop in frequency and were replaced by other SDDs (pentedrone, 3-MMC, methiopropamine, etc.). Newly identified compounds from seized materials were added to the list of new psychoactive substances ("Schedule C"). While the risk assessment of substances listed in Schedule C has to be performed within 2 years after scheduling, continuous monitoring of their presence and frequency among drug users is essential. In summary, our results suggest which substances should be dropped from the list of SDDs measured in biological samples; while the appearance of new substances from seized materials indicate the need for developing adequate standard analytical methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Drugs against avian influenza a virus: design of novel sulfonate inhibitors of neuraminidase N1.

    Science.gov (United States)

    Udommaneethanakit, Thanyarat; Rungrotmongkol, Thanyada; Frecer, Vladimir; Seneci, Pierfausto; Miertus, Stanislav; Bren, Urban

    2014-01-01

    The outbreak of avian influenza A (H5N1) virus has raised a global concern for both the animal as well as human health. Besides vaccination, that may not achieve full protection in certain groups of patients, inhibiting neuraminidase or the transmembrane protein M2 represents the main measure of controlling the disease. Due to alarming emergence of influenza virus strains resistant to the currently available drugs, development of new neuraminidase N1 inhibitors is of utmost importance. The present paper provides an overview of the recent advances in the design of new antiviral drugs against avian influenza. It also reports findings in binding free energy calculations for nine neuraminidase N1 inhibitors (oseltamivir, zanamivir, and peramivir -carboxylate, -phosphonate, and -sulfonate) using the Linear Interaction Energy method. Molecular dynamics simulations of these inhibitors were performed in a free and two bound states - the so called open and closed conformations of neuraminidase N1. Obtained results successfully reproduce the experimental binding affinities of the already known neuraminidase N1 inhibitors, i.e. peramivir being a stronger binder than zanamivir that is in turn stronger binder than oseltamivir, or phosphonate inhibitors being stronger binders than their carboxylate analogues. In addition, the newly proposed sulfonate inhibitors are predicted to be the strongest binders - a fact to be confirmed by their chemical synthesis and a subsequent test of their biological activity. Finally, contributions of individual inhibitor moieties to the overall binding affinity are explicitly evaluated to assist further drug development towards inhibition of the H5N1 avian influenza A virus.

  2. 21 CFR 316.29 - Revocation of orphan-drug designation.

    Science.gov (United States)

    2010-04-01

    ... sponsor's exclusive marketing rights for the drug but not the approval of the drug's marketing application... condition (or, in the case of vaccines, diagnostic drugs, or preventive drugs, the target population) is... the ground that the prevalence of the disease or condition (or the target population) becomes more...

  3. REFERENCE AID: Glossary of Spanish and Portuguese Narcotics Terms

    Science.gov (United States)

    1977-05-09

    rock form (IA) herramienta paraphernalia used to inject drugs (Ar) hierba marihuana (IA) hierba malefica marihuana (IA) hierbero marihuana "pusher...mona^ la monte mora morfeta morfinomano morisqueta mosca mostaza mota motado^ en moto motorolo mover mula nariguetazo ne stle neveria

  4. Structure-Based Drug Design of Small Molecule Peptide Deformylase Inhibitors to Treat Cancer

    Directory of Open Access Journals (Sweden)

    Jian Gao

    2016-03-01

    Full Text Available Human peptide deformylase (HsPDF is an important target for anticancer drug discovery. In view of the limited HsPDF, inhibitors were reported, and high-throughput virtual screening (HTVS studies based on HsPDF for developing new PDF inhibitors remain to be reported. We reported here on diverse small molecule inhibitors with excellent anticancer activities designed based on HTVS and molecular docking studies using the crystal structure of HsPDF. The compound M7594_0037 exhibited potent anticancer activities against HeLa, A549 and MCF-7 cell lines with IC50s of 35.26, 29.63 and 24.63 μM, respectively. Molecular docking studies suggested that M7594_0037 and its three derivatives could interact with HsPDF by several conserved hydrogen bonds. Moreover, the pharmacokinetic and toxicity properties of M7594_0037 and its derivatives were predicted using the OSIRIS property explorer. Thus, M7594_0037 and its derivatives might represent a promising scaffold for the further development of novel anticancer drugs.

  5. Design of a microemulsion-based drug delivery system for diclofenac sodium

    International Nuclear Information System (INIS)

    Kkizibash, N.A.; Asif, S.; Nazar, M.F.; Alenizi, D.; Shah, S.S.

    2011-01-01

    A microemulsion-based drug delivery system has been designed for Diclofenac Sodium(DS) comprising Span 60, 1-Propanol, Water, and Lemon Oil. The microemulsion system has been characterized by a pseudo-ternary phase diagram using the water titration method. The properties and structure of this system have been studied by the use of refractive index, electrical conductivity, viscosity and UV-Visible spectroscopy. The conductivity (s) and viscosity (k nu) measurements have provided evidence for percolation behavior with variation in F (weight fraction of aqueous phase). This phase transition corresponds to the structural change from water-in-oil to a bicontinuous microemulsion system. The percolation threshold (FC) obtained from conductivity measurements was in accordance with that obtained by viscosity measurements. Five microemulsion samples were selected and the changes in microstructure after incorporation of the drug, Diclofenac Sodium (DS) were examined by centrifugation, conductivity measurements, viscosity measurements and spectroscopic studies. The conductivity measurements showed that DS-loaded samples have higher conductivity values when compared to non-loaded samples. It was also found that DS is inter facially active. In addition, loading of DS had no negative effect on the stability of the system. (author)

  6. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Optimizing Oral Bioavailability in Drug Discovery: An Overview of Design and Testing Strategies and Formulation Options.

    Science.gov (United States)

    Aungst, Bruce J

    2017-04-01

    For discovery teams working toward new, orally administered therapeutic agents, one requirement is to attain adequate systemic exposure after oral dosing, which is best accomplished when oral bioavailability is optimized. This report summarizes the bioavailability challenges currently faced in drug discovery, and the design and testing methods and strategies currently utilized to address the challenges. Profiling of discovery compounds usually includes separate assessments of solubility, permeability, and susceptibility to first-pass metabolism, which are the 3 most likely contributors to incomplete oral bioavailability. An initial assessment of absorption potential may be made computationally, and high throughput in vitro assays are typically performed to prioritize compounds for in vivo studies. The initial pharmacokinetic study is a critical decision point in compound evaluation, and the importance of the effect the dosing vehicle or formulation can have on oral bioavailability, especially for poorly water soluble compounds, is emphasized. Dosing vehicles and bioavailability-enabling formulations that can be used for discovery and preclinical studies are described. Optimizing oral bioavailability within a chemical series or for a lead compound requires identification of the barrier limiting bioavailability, and methods used for this purpose are outlined. Finally, a few key guidelines are offered for consideration when facing the challenges of optimizing oral bioavailability in drug discovery. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Designing a Poly (N-isopropylacrylamide) Nanocapsule for Magnetic Field-assisted Drug Delivery

    Science.gov (United States)

    Denmark, Daniel; Mukherjee, Pritish; Witanachchi, Sarath

    2014-03-01

    The method of synthesis and the characteristics of polymer based nanocapsules as biomedical drug delivery systems are presented. Magnetic iron oxide nanoparticles have been incorporated into these capsules for effective guidance with external magnetic fields to transport therapeutic compounds to various parts of the human body. Once they have reached their destination they can be stimulated to release the drug to the target tissue through externally applied fields. The polymeric material that constitutes the capsules is specifically designed to melt away with the external stimuli to deliver the therapeutic bio agents near the target tissue. In this work we use nebulization to create aqueous poly (N-isopropylacrylamide) nanoparticles that decompose after being heated beyond their transition temperature. Transmission Electron Microscopic imaging (TEM) and dynamic light scattering (DLS) experiments have been conducted to study the decomposition of the capsules under external stimuli. Distribution of the magnetic nanoparticles within the capsules and their role in delivering the bio agents have been investigated by the Magnetic Force Microscopy (MFM).

  9. Designing cyclopentapeptide inhibitor as potential antiviral drug for dengue virus ns5 methyltransferase.

    Science.gov (United States)

    Idrus, Syarifuddin; Tambunan, Usman Sumo Friend; Zubaidi, Ahmad Ardilla

    2012-01-01

    NS5 methyltransferase (Mtase) has a crucial role in the replication of dengue virus. There are two active sites on NS5 Mtase i.e., SAM and RNA-cap binding sites. Inhibition of the NS5 Mtase activity is expected to prevent the propagation of dengue virus. This study was conducted to design cyclic peptide ligands as enzyme inhibitors of dengue virus NS5 Mtase through computational approach. Cyclopentapeptides were designed as ligand of SAM binding site as much as 1635 and 736 cyclopentpeptides were designed as ligand of RNA-cap binding site. Interaction between ligand and NS5 Mtase has been conducted on the Docking simulation. The result shows that cyclopentapeptide CTWYC was the best peptide candidate on SAM binding site, with estimated free binding energy -30.72 kca/mol. Cyclopentapeptide CYEFC was the best peptide on RNA-cap binding site with estimated free binding energy -22.89 kcal/mol. Both peptides did not have tendency toward toxicity properties. So it is expected that both CTWYC and CYEFC ligands could be used as a potential antiviral drug candidates, which can inhibit the SAM and RNA-cap binding sites of dengue virus NS5 Mtase.

  10. Design of Probabilistic Random Forests with Applications to Anticancer Drug Sensitivity Prediction.

    Science.gov (United States)

    Rahman, Raziur; Haider, Saad; Ghosh, Souparno; Pal, Ranadip

    2015-01-01

    Random forests consisting of an ensemble of regression trees with equal weights are frequently used for design of predictive models. In this article, we consider an extension of the methodology by representing the regression trees in the form of probabilistic trees and analyzing the nature of heteroscedasticity. The probabilistic tree representation allows for analytical computation of confidence intervals (CIs), and the tree weight optimization is expected to provide stricter CIs with comparable performance in mean error. We approached the ensemble of probabilistic trees' prediction from the perspectives of a mixture distribution and as a weighted sum of correlated random variables. We applied our methodology to the drug sensitivity prediction problem on synthetic and cancer cell line encyclopedia dataset and illustrated that tree weights can be selected to reduce the average length of the CI without increase in mean error.

  11. Opium and Afghanistan: Reassessing U.S. Counter-Narcotics Strategy

    Science.gov (United States)

    2007-03-30

    and effective governance of Afghanistan.”3 This paper examines the nature of the opium problem in Afghanistan and analyzes the current strategy to...Opium is also refined for use in legal prescription painkillers such as OxyContin and Vicodin.14 However, Australia and France currently produce about...is simply inadequate to carry out an effective counter-narcotics campaign. While some regions of Afghanistan are relatively stable and free of

  12. A Bayesian approach for incorporating economic factors in sample size design for clinical trials of individual drugs and portfolios of drugs.

    Science.gov (United States)

    Patel, Nitin R; Ankolekar, Suresh

    2007-11-30

    Classical approaches to clinical trial design ignore economic factors that determine economic viability of a new drug. We address the choice of sample size in Phase III trials as a decision theory problem using a hybrid approach that takes a Bayesian view from the perspective of a drug company and a classical Neyman-Pearson view from the perspective of regulatory authorities. We incorporate relevant economic factors in the analysis to determine the optimal sample size to maximize the expected profit for the company. We extend the analysis to account for risk by using a 'satisficing' objective function that maximizes the chance of meeting a management-specified target level of profit. We extend the models for single drugs to a portfolio of clinical trials and optimize the sample sizes to maximize the expected profit subject to budget constraints. Further, we address the portfolio risk and optimize the sample sizes to maximize the probability of achieving a given target of expected profit.

  13. Octreotide: a powerful non-narcotic analgesic for ocular instillation

    Directory of Open Access Journals (Sweden)

    Nicola Maratea

    2015-05-01

    Full Text Available The development of alternative substances for pain treatment is necessary for patients who cannot tolerate the side effects of opioids or cannot reach an adequate analgesia with these drugs. The technique using the endo-ocular instillation of drops, 2 ml of solution containing 0.05 mg of octreotide plus 1 ml of water for injectable preparations, thus obtaining a solution containing 0.025 mg / ml of octreotide, was instilled via a precision dropping that provided 0.00119 mg / drop of octreotide. Due to characteristics of pain, we administered the doses ranging from 1 to 3 drops per eye. The absence of side effects and the simplicity of execution have prompted to consider this method with extreme interest, in order to research the drugs and routes of administration which follow more the conditions of tolerability and selectivity of effects.

  14. Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery

    Czech Academy of Sciences Publication Activity Database

    Tykvart, Jan; Schimer, Jiří; Bařinková, Jitka; Pachl, Petr; Poštová Slavětínská, Lenka; Majer, Pavel; Konvalinka, Jan; Šácha, Pavel

    2014-01-01

    Roč. 22, č. 15 (2014), s. 4099-4108 ISSN 0968-0896 R&D Projects: GA ČR GBP208/12/G016 Grant - others:OPPK(CZ) CZ.2.16/3.1.00/24016 Institutional support: RVO:61388963 Keywords : GCPII * PSMA * structure-aided drug design * specific drug targeting Subject RIV: CE - Biochemistry Impact factor: 2.793, year: 2014

  15. Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E (“Europa”)

    OpenAIRE

    Sacks, Justin; Ray, M. Jordan; Williams, Sue; Opatowsky, Michael J.

    2012-01-01

    We present a case of a fatal toxic leukoencephalopathy following ingestion of a new psychoactive designer drug known as 2C-E or “Europa.” Recreational drugs, particularly hallucinogenic substances, appear to be growing in popularity, with increasing amounts of information available via the Internet to entice potential users. In addition, some newer “designer” psychoactive substances are available for purchase online without adverse legal consequences, therefore adding to their popularity. We ...

  16. [The issue of harm reduction in Polish legislation concerning drug addiction. A comparative study].

    Science.gov (United States)

    Sobeyko, Justyna

    2008-01-01

    The aim of work is the assessment of legal permissibility for health and social harm reduction programmes resulting from drug use in the context of the polish legislation on narcotic drug use and drug addiction. The thesis outlines harm reduction programmes implemented worldwide, role of penal code in counteracting both narcotic drug supply and demand, attitude of United Nations and European Union to the drug problem including harm reduction programmes, solutions adopted in the selected European Union member states. The main part of the thesis presents the evolution of polish legislation regarding drug use and analysis of legal permissibility for harm reduction programmes in this context. The conclusion inferred is the statement that implementation of the harm reduction programmes requires a certain minimal depenalisation of the drug use by a legislator and the fact that restrictive legal system impedes programme realization. Thus the thesis postulates depenalisation of small drug quantities for personal use.

  17. GREEN: A program package for docking studies in rational drug design

    Science.gov (United States)

    Tomioka, Nobuo; Itai, Akiko

    1994-08-01

    A program package, GREEN, has been developed that enables docking studies between ligand molecules and a protein molecule. Based on the structure of the protein molecule, the physical and chemical environment of the ligand-binding site is expressed as three-dimensional grid-point data. The grid-point data are used for the real-time evaluation of the protein-ligand interaction energy, as well as for the graphical representation of the binding-site environment. The interactive docking operation is facilitated by various built-in functions, such as energy minimization, energy contribution analysis and logging of the manipulation trajectory. Interactive modeling functions are incorporated for designing new ligand molecules while considering the binding-site environment and the protein-ligand interaction. As an example of the application of GREEN, a docking study is presented on the complex between trypsin and a synthetic trypsin inhibitor. The program package will be useful for rational drug design, based on the 3D structure of the target protein.

  18. The Use of Stilbene Scaffold in Medicinal Chemistry and Multi- Target Drug Design.

    Science.gov (United States)

    Giacomini, Elisa; Rupiani, Sebastiano; Guidotti, Laura; Recanatini, Maurizio; Roberti, Marinella

    2016-01-01

    The stilbene scaffold is a basic element for a number of biologically active natural and synthetic compounds, and it is considered as a privileged structure. Stilbenes exemplified by resveratrol, combretastatin A-4 and pterostilbene are of significant interest for drug research and development because of their potential in therapeutic and preventive application. Resveratrol, present in grapes and other food products, plays a role in the prevention of several human pathological processes and has been suggested as an anticancer agent. Moreover, recent evidence has revealed its potential effect on the aging process, diabetes and neurological dysfunction. Combretastatin A-4, from the bark of South African bush willow Combretum caffrum, also shows significant antitumor activity. Pterostilbene is closely related to resveratrol, sharing the same unique therapeutic potential as anti-inflammatory, antineoplastic and antioxidant agent. Therefore, research and development of stilbene-based medicinal chemistry have become rapidly evolving and increasingly active topics covering almost the whole range of therapeutic fields. In the present review, we provide an overview of the role of stilbenes in medicinal chemistry. In this context, we highlight the chemical methodologies adopted for the synthesis of stilbene derivatives, and outline the successful design of novel stilbene based hybrids in the field of cancer, Alzheimer's and other relevant diseases. This information may be useful in further design of stilbene-based molecules as new leads for the development of novel agents with clinical potential or as effective chemical probes to dissect biological processes.

  19. Identification of anthranilamide derivatives as potential factor Xa inhibitors: drug design, synthesis and biological evaluation.

    Science.gov (United States)

    Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin

    2015-05-05

    The coagulation enzyme factor Xa (fXa) plays a crucial role in the blood coagulation cascade. In this study, three-dimensional fragment based drug design (FBDD) combined with structure-based pharmacophore (SBP) model and structural consensus docking were employed to identify novel fXa inhibitors. After a multi-stage virtual screening (VS) workflow, two hit compounds 3780 and 319 having persistent high performance were identified. Then, these two hit compounds and several analogs were synthesized and screened for in-vitro inhibition of fXa. The experimental data showed that most of the designed compounds displayed significant in vitro potency against fXa. Among them, compound 9b displayed the greatest in vitro potency against fXa with the IC50 value of 23 nM and excellent selectivity versus thrombin (IC50 = 40 μM). Moreover, the prolongation of the prothrombin time (PT) was measured for compound 9b to evaluate its in vitro anticoagulant activity. As a result, compound 9b exhibited pronounced anticoagulant activity with the 2 × PT value of 8.7 μM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. Tailored approaches in drug development and diagnostics : from molecular design to biological model systems

    NARCIS (Netherlands)

    Sahlgren, C.M.; Meinander, A.; Zhang, H.; Cheng, F.; Preis, Maren; Xu, C.; Salminen, T.A.; Toivola, D.M.; Abankwa, D.; Rosling, A.; Karaman, D.Ş.; Salo-Ahen, O.M.H.; Österbacka, R.; Eriksson, J.E.; Willför, S.; Petre, I.; Peltonen, J.; Leino, R.; Johnson, M.; Rosenholm, J.; Sandler, N.

    2017-01-01

    Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic