Sample records for dibucaine

  1. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Jun Liu


    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  2. [Frequency distribution of dibucaine numbers in 24,830 patients].

    Pestel, G; Sprenger, H; Rothhammer, A


    Atypical cholinesterase prolongs the duration of neuromuscular blocking drugs such as succinylcholine and mivacurium. Measuring the dibucaine number identifies patients who are at risk. This study shows the frequency distribution of dibucaine numbers routinely measured and discusses avoidable clinical problems and economic implications. Dibucaine numbers were measured on a Hitachi 917-analyzer and all dibucaine numbers recorded over a period of 4 years were taken into consideration. Repeat observations were excluded. A total of 24,830 dibucaine numbers were analysed and numbers below 30 were found in 0.07% ( n=18) giving an incidence of 1:1,400. Dibucaine numbers from 30 to 70 were found in 1.23% ( n=306). On the basis of identification of the Dibucaine numbers we could avoid the administration of succinylcholine or mivacurium resulting in a cost reduction of 12,280 Euro offset against the total laboratory costs amounting to 10,470 Euro. An incidence of 1:1,400 of dibucaine numbers below 30 is higher than documented in the literature. Therefore, routine measurement of dibucaine number is a cost-effective method of identifying patients at increased risk of prolonged neuromuscular blockade due to atypical cholinesterase.

  3. Release characteristics of dibucaine dispersed in konjac gels.

    Nakano, M; Takikawa, K; Arita, T


    A possible use of konjac gel for sustained release of drugs was examined in a monolithic system containing dibucaine. Dibucaine was dispersed in the gel which was prepared by gelation of the konjac flour in a borax solution at 60 degrees. The cumulative amount of the drug released plotted against the square root of time was linear in the monolithic system. This relationship was in agreement with that expected from the theoretical equation for planar configuration. The mechanism of the release of the drug from the gel may be considered to be leaching of the drug by the permeating fluid. The release profile from dried konjac gel was similar to that from undried gel, but that from unwarmed gel showed a deviation from linearity although sustained release was similarly obtained.

  4. Relaxation dynamics of amorphous dibucaine using dielectric studies

    Sahra, M.; Jumailath, K.; Thayyil, M. Shahin; Capaccioli, S.


    Using broadband dielectric spectroscopy the molecular mobility of dibucaine is investigated in the supercooled liquid and gassy states, over a wide temperature range for some test frequencies. Above the glass transition temperature Tg, the presence of structural α- relaxation peak was observed due to the cooperative motions of the molecule and upon cooling frozen kinetically to form the glass. The secondary relaxation process was perceivable below Tg due to localized motions. The peak loss frequency of α-relaxation process shows non-Arrhenius behavior and obeys Vogel-Fulcher-Tammann equation over the measured temperature range whereas the β- process shows Arrhenius behavior.

  5. A competitive strategy based on cucurbit[7]uril supramolecular interaction for simple and sensitive detection of dibucaine.

    Li, Yan; Li, Chang-Feng; Du, Li-Ming; Feng, Jian-Xia; Liu, Hai-Long; Fu, Yun-Long


    In this work, the competitive interaction between dibucaine and three fluorescent probes (i.e., berberine, palmatine, and coptisine) for occupancy of the cucurbit[7]uril (CB[7]) cavity was studied by fluorescence spectra, UV-visible absorption spectra, (1)H NMR spectra, and theoretical calculations in acidic aqueous solution. Based on the fluorescence enhancement of berberine, palmatine, and coptisine upon binding with CB[7], respectively, a series of fluorescence detection methods for dibucaine were proposed. At the optimized conditions, the fluorescence intensity of berberine-CB[7], palmatine-CB[7], and coptisine-CB[7] complexes showed negative correlation to the concentration of dibucaine, which led to a series of simple and sensitive fluorescence methods for the determination of dibucaine for the first time. Linear ranges obtained in the detection of the dibucaine were 0.018-3.34 μmol L(-1), 0.032-4.47 μmol L(-1), and 0.079-4.42 μmol L(-1) with detection limits of 6.0 nmol L(-1), 12.0 nmol L(-1), and 25.0 nmol L(-1), respectively. Moreover, the proposed method was successfully applied for the determination of the drug in biological fluids. The competitive mode based on CB[7] superstructure provided a promising assay strategy for fluorescence detection in various potential applications.

  6. In vitro release of dibucaine hydrochloride from chitosan semisolid vehicles: emulsion and hydrophilic gels

    Nilia de la Paz


    Full Text Available Context: Chitosan has received attention as a functional, sustainably renewable, nontoxic and biodegradable biopolymer for pharmaceutical applications. Aims: To evaluate the release of dibucaine hydrochloride from semisolid vehicles of oil/aqueous type emulsion and aqueous gels, stabilized by using chitosan (CH or chitosan acetate (CHAc. Methods: Emulsions were developed by varying the emulsifying agent: polysorbate 80, CH or CHAc and by combining CH with polysorbate 80 or CHAc with polysorbate 80. The hydroxypropylmethyl cellulose F4M was added as a stabilizing agent in gel formulations. The release rates of model drug from semisolid vehicles were measured by using a dialysis sac. Drug release was also quantified by using a validated UV-VIS spectrophotometric method. Results: The pH values showed minimal changes for emulsion and gel formulations. The drug is a cationic salt, and it is not able to bind polymer cations by electrostatic repulsion. The rheological property of the vehicle type emulsion was adjusted to plastic and pseudo-plastic fluid to the gels. The drug release was independent of the viscosity of vehicles. Dibucaine release from both types of formulation was found to follow a square-root-of-time kinetic model, but a higher rate of release was obtained from gel formulations. Conclusions: It was shown that chitosan was adsorbed to the surface of polysorbate 80-coated droplets, and that the electrostatic attraction between the non-ionic surfactant and the drug retarded its release from a semisolid system. The multilayer emulsions showed more influence of the release of drug than CH or CHAc single layer emulsion.

  7. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

    W Christopher Risher

    Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

  8. Cytotoxicity of solid lipid nanoparticles and nanostructured lipid carriers containing the local anesthetic dibucaine designed for topical application

    Barbosa, R. M.; da Silva, C. M. G.; Bella, T. S.; de Araújo, D. R.; Marcato, P. D.; Durán, N.; de Paula, E.


    Dibucaine (DBC) is powerful long-lasting local anesthetic, but it is also considered fairly toxic to the CNS. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have attracted attention as carriers for drug delivery. The aim of this study was to develop and to evaluate the cytotoxic activity of DBC-loaded SLN and NLC against 3T3 fibroblast and HaCat keratinocyte cells. The SLN and NLC had myristyl myristate and Liponate®GC as their lipid matrices, respectively, plus a surfactant. SLN and NLC were characterized in terms in their diameter, size distribution, surface charge and DBC encapsulation efficiency. The particle size of SLN and NLC were around 234.33 and 166.62 nm, respectively. The polydispersity index was kept below 0.2 for both nanomaterials. Negative surface charges were observed for both nanoparticles, which decreased in the presence of the anesthetic. Encapsulation efficiency reached 76% and 90%, respectively, in SLN and NLC. DBC alone was found to be toxic to 3T3 and HaCat cells in culture. However, NLC and SLN loaded DBC decreased its intrinsic cytotoxic effect against 3T3 and HaCat cells. In conclusion, encapsulation of DBC in SLN and NLC decreased the in vitro toxicity of the local anesthetic, indicating the potential of these nanocarriers for clinical applications.

  9. Prolonged Paralysis Following Emergent Cesarean Section with Succinylcholine Despite Normal Dibucaine Number.

    Ellison, Matthew; Grose, Brian; Howell, Stephen; Wilson, Colin; Lenz, Jackson; Driver, Richard


    Prolonged paralysis due to a quantitative or qualitative deficiency of pseudocholinesterase activity is an uncommon but known side effect of succinylcholine. We describe a patient who experienced prolonged paralysis following administration of succinylcholine for general anesthesia and endotracheal intubation for an emergent cesarean section despite laboratory evidence of normal enzyme function. The patient required mechanical ventilation in the intensive care unit for several hours following surgery. The patient was extubated following return of full muscle strength and had a good outcome. The enzyme responsible for the metabolism of succinylcholine, pseudocholinesterase, was determined to be low in quantity in this patient but was functionally normal. This low level, by itself, was unlikely to be solely responsible for the prolonged paralysis. The patient likely had an abnormal pseudocholinesterase enzyme variant that is undetectable by standard laboratory tests.

  10. Drug: D04699 [KEGG MEDICUS

    Full Text Available D04699 Mixture, Drug Hydrocortisone - fradiomycin sulfate - dibucaine hydrochloride... - esculoside mixt; Proctosedyl (TN) Hydrocortisone [DR:D00088], Fradiomycin sulfate [DR:D01618], Dibucaine ...organ agents 255 Hemorrhoidal preparations 2559 Others D04699 Hydrocortisone - fradiomycin sulfate - dibucaine hydrochloride - esculoside mixt PubChem: 17398142 ...

  11. Drug: D04844 [KEGG MEDICUS

    Full Text Available D04844 Mixture, Drug Paraformaldehyde - dibucaine hydrochloride mixt; Periodon (TN)... Paraformaldehyde [DR:D01494], Dibucaine hydrochloride [DR:D02220] Therapeutic category: 2730 Therapeutic category of dr...sics and sedatives 2730 Analgesics and sedatives D04844 Paraformaldehyde - dibucaine hydrochloride mixt CAS: 617-48-1 PubChem: 17398192 NIKKAJI: J237.180D ...

  12. Drug: D02220 [KEGG MEDICUS

    Full Text Available D02220 Drug Dibucaine hydrochloride (JP16/USP); Nupercaine hydrochloride (TN); Perc...amin (TN) C20H29N3O2. HCl 379.2027 379.9241 D02220.gif Anesthetic [local] Therapeutic category: 1213 ATC cod... nervous system and sensory organs 12 Agents affecting peripheral nervous system 121 Local anesthetics 1213 Dibucaines D02220...OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE C05AD Local anesthetics C05AD04 Cinchocaine D02220 Dibucain...ical use D04AB02 Cinchocaine D02220 Dibucaine hydrochloride (JP16/USP) N NERVOUS SYSTEM N01 ANESTHETICS N01B

  13. Drug: D04053 [KEGG MEDICUS

    Full Text Available D04053 Mixture, Drug Dibucaine hydrochloride - p-butylaminobenzoyldiethylaminoethyl hydr...ochloride mixt; Neo-percamin S (TN) Dibucaine hydrochloride [DR:D02220], p-Butylaminobenzoyldiethylaminoethyl hydr...ochloride [DR:D01967] Therapeutic category: 1219 Therapeutic category of drugs in Japan [BR:br083...pheral nervous system 121 Local anesthetics 1219 Others D04053 Dibucaine hydrochloride - p-butylaminobenzoyldiethylaminoethyl hydrochloride mixt PubChem: 17398017 ...

  14. Drug: D04707 [KEGG MEDICUS

    Full Text Available D04707 Mixture, Drug Lithospermum root extract - ethyl aminobenzoate - dibucaine hydrochloride - diphenhydr...amine hydrochloride - cetrimide mixt; Borraginol N (TN) Lithospermum root extract [D...R:D04705], Ethyl aminobenzoate [DR:D00552], Dibucaine hydrochloride [DR:D02220], Diphenhydramine hydrochloride [DR:D00669], Cetrimide [DR:D02164] PubChem: 17398145 ...

  15. Drug: D04022 [KEGG MEDICUS

    Full Text Available D04022 Mixture, Drug Sodium salicylate - dibucaine hydrocholoride - calcium bromide... mixt; Neo vitacain (TN) Sodium salicylate [DR:D00566], Dibcaine hydrochloride [DR:D02220], Calcium bromide ...[DR:D01723] Anti-inflammatory Therapeutic category: 1149 Therapeutic category of drugs in Japan [BR:br08301]... nervous system 114 Antipyretics and analgesics, anti-inflammatory agents 1149 Others D04022 Sodium salicylate - dibucaine hydrocholoride - calcium bromide mixt PubChem: 17398006 ...

  16. Drug: D04819 [KEGG MEDICUS

    Full Text Available D04819 Mixture, Drug Arsenic trioxide - dibucaine hydrochloride - dl-methylephedrine hydr...ochloride - p-butylaminobenzoyldiethylaminoethyl hydrochloride - benzyl alcohol mixt; Neoarsen black (...TN) Arsenic trioxide [DR:D02106], Dibucaine hydrochloridide [DR:D02220], dl-Methylephedrine hydrochloride [D...R:D02109], p-Butylaminobenzoyldiethylaminoethyl hydrochloride [DR:D01967], Benzyl alcohol [DR:D00077] PubChem: 17398187 ...

  17. Drug: D00733 [KEGG MEDICUS

    Full Text Available AGENTS FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE C05AD Local anesthetic...ICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04A ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04AB Anesthetic... Dibucaine (USP); Cinchocaine (INN) S SENSORY ORGANS S01 OPHTHALMOLOGICALS S01H LOCAL ANESTHETICS S01HA Local anesthetic...GICALS S02DA Analgesics and anesthetics S02DA04 Cinchocaine D00733 Dibucaine (USP...hetic [local] Same as: C07879 ATC code: C05AD04 D04AB02 N01BB06 S01HA06 S02DA04 vol

  18. Pseudocholinesterase in the serum of allergic subjects

    Berrens, L.; Dijk, A.G. van


    There are no differences, between human normal and allergic sera, in the total activity of naphthylacetate-hydrolysing enzymes. No abnormal dibucaine-inhibited isoenzymes were detected. The Michaelis constants and the activation energies of serum pseudocholinesterases in the sera of patients with

  19. Pseudocholinesterase in the serum of allergic subjects

    Berrens, L.; Dijk, A.G. van


    There are no differences, between human normal and allergic sera, in the total activity of naphthylacetate-hydrolysing enzymes. No abnormal dibucaine-inhibited isoenzymes were detected. The Michaelis constants and the activation energies of serum pseudocholinesterases in the sera of patients with at

  20. Effects of tertiary amine local anesthetics on the assembly and disassembly of brain microtubules in vitro.

    Genna, J M; Coffe, G; Pudles, J


    From kinetic and electron microscopy studies on the effects of procaine, tetracaine and dibucaine on the polymerization and depolymerization of the microtubules isolated from pig and rat brains the following results were obtained. 1. Procaine or tetracaine, at the concentration range of 0.5--20 mM and of 0.5--5 mM respectively, increases the rate of tubulin polymerization (24 degrees C or 37 degrees C) and of microtubule depolymerization (4 degrees C) as a linear function of the concentration of the anesthetics, while identical amounts of microtubules are formed. In the absence of microtubule-associated proteins the polymerization of tubulin is not induced by 10 mM procaine, furthermore, the critical concentration of microtubule proteins necessary for assembly into microtubules is not affected at this concentration level of the anesthetic. This suggests that procaine affects not the nucleation, but rather the elongation process. 2. Dibucaine, from 0.5 mM to 3 mM increases the lag time of the polymerization reaction, while from 0.5 mM to 2 mM it linearly decreases both tubulin polymerization (24 degrees C) and microtubule depolymerization (4 degrees C) rates. Dibucaine, up to mM concentration, does not affect the extent of tubulin polymerization; however, above this concentration it induces the formation of amorphous aggregates. 3. Procaine or tetracaine enhances the depolymerizing effect of calcium on microtubules. The half-maximal values for the depolymerizing effect of calcium were 0.96, 0.71 and 0.51 mM for the control, in the presence of 10 mM procaine and 5 mM tetracaine respectively.

  1. Chromatography of crotamiton and its application to the determination of active ingredients in ointments.

    Izumoto, S; Machida, Y; Nishi, H; Nakamura, K; Nakai, H; Sato, T


    Crotamiton, which is a mixture of cis and trans isomers, was investigated by several separation techniques. One of the HPLC modes, in which crotamiton eluted as a single peak, was selected for the determination of five active ingredients (crotamiton, prednisolone, glycyrrhetinic acid, dibucaine and chlorhexidine hydrochloride) in an ointment. The simultaneous determination was performed using isocratic reversed-phase mode within 20 min by employing an octyl (C8) column and a mobile phase containing sodium dodecyl sulfate (SDS) and 2-propanol. The method was successfully applied to quality control and stability testing of the ointment.

  2. p-Bromophenacyl bromide prevents cumene hydroperoxide-induced mitochondrial permeability transition by inhibiting pyridine nucleotide oxidation.

    Zhukova, A; Gogvadze, G; Gogvadze, V


    Mitochondrial permeability transition is commonly characterized as a Ca2+ -dependent non-specific increase in inner membrane permeability that results in swelling of mitochondria and their de-energization. In the present study, the effect of different inhibitors of phospholipase A2--p-bromophenacyl bromide, dibucaine, and aristolochic acid--on hydroperoxide-induced permeability transitions in rat liver mitochondria was tested. p-Bromophenacyl bromide completely prevented the hydroperoxide-induced mitochondrial permeability transition while the effects of dibucaine or aristolochic acid were negligible. Organic hydroperoxides added to mitochondria undergo reduction to corresponding alcohols by mitochondrial glutathione peroxidase. This reduction occurs at the expense of GSH which, in turn, can be reduced by glutathione reductase via oxidation of mitochondrial pyridine nucleotides. The latter is considered a prerequisite step for mitochondrial permeability transition. Among all the inhibitors tested, only p-bromophenacyl bromide completely prevented hydroperoxide-induced oxidation of mitochondrial pyridine nucleotides. Interestingly, p-bromophenacyl bromide had no affect on mitochondrial glutathione peroxidase, but reacted with mitochondrial glutathione that prevented pyridine nucleotides from being oxidized. Our data suggest that p-bromophenacyl bromide prevents hydroperoxide-induced deterioration of mitochondria via interaction with glutathione rather than through inhibition of phospholipase A2.

  3. [Spread of spinal anesthesia with 3 different hyperbaric solutions used in Japan].

    Masuda, R; Yokoyama, K; Inoue, T


    We studied the spread of spinal anesthesia with 3 different hyperbaric solutions commercially available in Japan. Percamin-S [0.3% dibucaine in 5% hyperbaric saline] (P), Neo-Percamin.S [0.24% dibucaine with 0.12% T-caine in 9.5% glucose] (N) and 0.5% Tetcaine [tetracaine] in 10% glucose (T) were studied. Two ml of each solution was administered intrathecally using a 25 gauge Quincke needle. Patients (n = 90) were allocated to one of 9 groups receiving 2 ml of P, N or T at L 2-3, L 3-4 or L 4-5 interspace. Both N and T produced significantly higher spread of analgesia than P at any of L 3-4 and L 4-5 interspaces. P and N have the same specific gravity, even though significant differences were found in spread of segmental analgesia. Local anesthesic agents and solvent solutions themselves are considered to influence the spread of spinal anesthesia as the specific gravity of hyperbaric solution does.

  4. History of T-cain: a local anesthetic developed and manufactured in Japan.

    Tobe, Masaru; Saito, Shigeru


    In many anesthesia textbooks written in English, lidocaine, tetracaine, bupivacaine, ropivacaine, and chloroprocaine are listed as useful local anesthetics for spinal anesthesia. In contrast, T-cain is not included in these lists, even though it has been reported to be suitable for spinal anesthesia in Japan. T-cain was developed as a local anesthetic in the early 1940s by Teikoku Kagaku Sangyo Inc. in Itami, Japan, by replacing a methyl group on tetracaine (Pantocaine(®)) with an ethyl group. T-cain was clinically approved for topical use in Japan in November 1949, and a mixture of dibucaine and T-cain (Neo-Percamin S(®)) was approved for spinal use in May 1950. Simply because of a lack of foreign marketing strategy, T-cain has never attracted global attention as a local anesthetic. However, in Japan, T-cain has been used topically or intrathecally (as Neo-Percamin S(®)) for more than 60 years. Other than the side effects generally known for all local anesthetics, serious side effects have not been reported for T-cain. In fact, several articles have reported that T-cain decreases the neurotoxicity of dibucaine. In this historical review, the characteristics of T-cain and its rise to become a major spinal anesthetic in Japan are discussed.

  5. Reconstitution of neurotoxin-modulated ion transport by the voltage-regulated sodium channel isolated from the electroplax of Electrophorus electricus.

    Rosenberg, R L; Tomiko, S A; Agnew, W S


    The functional reconstitution of the voltage-regulated Na channel purified from the electroplax of Electrophorus electricus is described. Reconstitution was achieved by removing detergent with Bio-Beads SM-2 followed by freeze-thaw-sonication in the presence of added liposomes. This preparation displayed heat-stable binding of 3H-labeled tetrodotoxin (TTX) (Kd = 33 nM). 22Na+ influx was stimulated 2- to 5-fold by alkaloid neurotoxins and blocked by TTX. Veratridine activated Na+ influx with a K1/2 of 18 microM, and this activation was blocked by TTX precisely in parallel with specific [3H]TTX binding. Batrachotoxin stimulated 22Na+ flux more effectively than did veratridine. No effect of the peptide anemone toxin II was found. Insertion of the Na channel into membranes resulted in 60-70% of the TTX-binding sites facing the vesicle exterior. Thus, external TTX partially inhibited flux, whereas blockade was complete when TTX was also equilibrated with the vesicle interior. The lipid-soluble local anesthetics tetracaine and dibucaine inhibited flux completely. QX-222, a charged derivative of lidocaine, blocked only a fraction of the channels, apparently those oriented inside-out. Purified samples were predominantly composed of the Mr 260,000-300,000 glycopeptide but contained variable quantities of smaller peptides. Veratridine-dependent flux and peptide compositions were determined on fractions across a gel filtration column profile. Stimulated flux codistributed only with the large peptide. Images PMID:6322191

  6. Enhancement of the 1-Octanol/Water Partition Coefficient of the Anti-Inflammatory Indomethacin in the Presence of Lidocaine and Other Local Anesthetics.

    Tateuchi, Ryo; Sagawa, Naoki; Shimada, Yohsuke; Goto, Satoru


    Side effects and excessive potentiation of drug efficacy caused by polypharmacy are becoming important social issues. The apparent partition coefficient of indomethacin (log P'IND) increases in the presence of lidocaine, and this is used as a physicochemical model for investigating polypharmacy. We examined the changes in log P'IND caused by clinically used local anesthetics-lidocaine, tetracaine, mepivacaine, bupivacaine, and dibucaine-and by structurally similar basic drugs-procainamide, imipramine, and diltiazem. The quantitative structure-activity relationship study of log P'IND showed that the partition coefficient values (log PLA) and the structural entropic terms (ΔSobs, log f) of the additives affect log P'IND. These results indicate that the local anesthetics and structurally similar drugs function as phase-transfer catalysts, increasing the membrane permeability of indomethacin via heterogeneous intermolecular association. Therefore, we expect that the potency of indomethacin, an acidic nonsteroidal anti-inflammatory drug, will be increased by concurrent administration of the other drugs.

  7. Inhibition of human plasma and serum butyrylcholinesterase (EC by alpha-chaconine and alpha-solanine.

    Nigg, H N; Ramos, L E; Graham, E M; Sterling, J; Brown, S; Cornell, J A


    The purpose of these experiments was to determine the reversibility of alpha-chaconine and alpha-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate alpha-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 x 10(-4) M. Dibucaine (1 x 10(-5) M) indicated the usual phenotype for all subjects; alpha-chaconine and alpha-solanine at 2.88 x 10(-6) M inhibited BuChE about 70 and 50%, respectively. One- and 24-hr incubations at 1 x 10(-5) M with alpha-chaconine, alpha-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1- and 24-hr incubations also showed no inhibition except for paraoxon. alpha-Chaconine and alpha-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, alpha-chaconine, alpha-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined alpha-chaconine, alpha-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin alpha-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is discussed.

  8. Determination of tolperisone in human plasma by liquid chromatography/tandem mass spectrometry for clinical application.

    Choi, Chang-Ik; Park, Jung-In; Lee, Hye-In; Lee, Yun-Jeong; Jang, Choon-Gon; Bae, Jung-Woo; Lee, Seok-Yong


    We have developed and validated a simple, rapid, and sensitive liquid chromatography analytical method employing tandem mass spectrometry (LC-MS/MS) for the determination of tolperisone, a centrally acting muscle relaxant, in human plasma. After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of tolperisone was performed using a reversed-phase Luna C(18) column (2.0mm×50mm, 5μm particles) with a mobile phase of 10mM ammonium formate buffer (pH 3.5) - methanol (12:88, v/v) and quantified by tandem mass detection in ESI positive ion mode. The flow rate of the mobile phase was 250μL/min and the retention times of tolperisone and the internal standard (IS, dibucaine) were both 0.6min. The calibration curves were linear over a range of 0.5-300ng/mL (r>0.999). The lower limit of quantification, using 200μL human plasma, was 0.5ng/mL. The mean accuracy and precision for intra- and inter-day validation of tolperisone were within acceptable limits. The LC-MS/MS method reported here showed improved sensitivity for quantification of tolperisone in human plasma compared with previously described analytical methods. Lastly, the validated method was successfully applied to a pharmacokinetic study in humans.

  9. Characterization of Deciliation-Regeneration Process of Tetrahymena Pyriformis for Cellular Robot Fabrication

    Dal Hyung Kim; Sean E. Brigandi; Paul Kim; Doyoung Byun; Min Jun Kim


    Artificial magnetotactic Tetrahymena pyriformis GL (T. pyriformis) cells were created by the internalization of iron oxide nano particles and became controllable with a time-varying external magnetic field. Thus, T. pyriformis can be utilized as a cellular robot to conduct micro-scale tasks such as transportation and manipulation. To complete these tasks, loading inorganic or organic materials onto the cell body is essential, but functionalization of the cell membrane is obstructed by their motile organelles, cilia. Dibucaine HCl, a local anesthetic, removes the cilia from the cell body, and the functional group would be absorbed more efficiently during cilia regeneration. In this paper, we characterize the recovery of artificial magnetotactic T.pyriformis after the deciliation process to optimize a cellular robot fabrication process. After sufficient time to recover, the motility rate and the average velocity of the deciliated cells were six and ten percent lower than that of non-deciliated cells, respectively. We showed that the motile cells after recovery can still be controlled using magnetotaxis, making T. pyriformis a good candidate to be used as a cellular robot.

  10. Interactions of some local anesthetics and alcohols with membranes.

    Frangopol, P T.; Mihăilescu, D


    A review of the results obtained by our group in the last decade regarding the interactions of procaine, lidocaine, dibucaine and tetracaine with membranes is presented in the context of the literature data. The action upon membranes, in first approximation monomolecular film of stearic acid spread at the air/water interface used as a membrane model, the modification of biomembrane structure and function using diffraction methods, lipid phase transition, fluidity of lipids and proteins, membrane expansion and platelet aggregation were studied. The thermodynamic knowledge of membrane-alcohol interactions improved by using highly sensitive calorimetric techniques are briefly reported. One of the main conclusions is that the physical state of a monolayer model membrane was the result of competitive interactions between film-film and film-substrate interactions. It was taken into account that local anesthetics, such as lidocaine, carbisocaine, mesocaine, showed changes in the bilayer structure, reflected in macroscopic mechanical properties. This restructuring of the lipid bilayer has a significant influence on the operation of functional subunits, e.g. ionic channels formed by gramicidin. The results support the concept of non-specific interactions of local anesthetics with lipid bilayers. The theoretical modeling of the interactions of local anesthetics is closely compared with experimental data. Our new theory of relaxation for these interactions is using a non-archimedean formalism based on a process resulting from superpositions of different component processes which take place at different scales of time.

  11. Dual effect of local anesthetics on the function of excitable rod outer segment disk membrane

    Mashimo, T.; Abe, K.; Yoshiya, I.


    The effects of local anesthetics and a divalent cation, Ca2+, on the function of rhodopsin were estimated from the measurements of light-induced proton uptake. The light-induced proton uptake by rhodopsin in the rod outer segment disk membrane was enhanced at lower pH (4) but depressed at higher pHs (6 to 8) by the tertiary amine local anesthetics lidocaine, bupivacaine, tetracaine, and dibucaine. The order of local anesthetic-induced depression of the proton uptake followed that of their clinical anesthetic potencies. The depression of the proton uptake versus the concentration of the uncharged form of local anesthetic nearly describes the same curve for small and large dose of added anesthetic. Furthermore, a neutral local anesthetic, benzocaine, depressed the proton uptake at all pHs between 4 and 7. These results indicate that the depression of the proton uptake is due to the effect of only the uncharged form. It is hypothesized that the uncharged form of local anesthetics interacts hydrophobically with the rhodopsin in the disk membrane. The dual effect of local anesthetics on the proton uptake, on the other hand, suggests that the activation of the function of rhodopsin may be caused by the charged form. There was no significant change in the light-induced proton uptake by rhodopsin when 1 mM of Ca2+ was introduced into the disk membrane at varying pHs in the absence or presence of local anesthetics. This fact indicates that Ca2+ ion does not influence the diprotonating process of metarhodopsin; neither does it interfere with the local anesthetic-induced changes in the rhodopsin molecule.

  12. Characterization of a novel BCHE "silent" allele: point mutation (p.Val204Asp causes loss of activity and prolonged apnea with suxamethonium.

    Herve Delacour

    Full Text Available Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp. Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a "silent" phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 µM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels.

  13. New procedure to synthesize silver nanoparticles and their interaction with local anesthetics

    Mocanu A


    Full Text Available Aurora Mocanu,1 Roxana Diana Pasca,1 Gheorghe Tomoaia,2 Corina Garbo,1 Petre T Frangopol,1 Ossi Horovitz,1 Maria Tomoaia-Cotisel11Chemical Engineering Department, Babes-Bolyai University, 2Orthopedic Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, RomaniaAbstract: Silver nanoparticles (AgNPs were prepared in aqueous colloid dispersions by the reduction of Ag+ with glucose in alkaline medium. Tetraethyl orthosilicate and l-asparagine were added as stabilizers of NPs. The AgNPs were characterized, and their interaction with three local anesthetics (procaine, dibucaine, or tetracaine was investigated. Optical spectra show the characteristic absorption band of AgNPs, due to surface plasmon resonance. Modifications in the position and shape of this band reflect the self-assembly of metal NPs mediated by anesthetic molecules and the progress in time of the aggregation process. Zeta-potential measuring was applied in order to characterize the electrostatic stability of the NPs. The size and shape of the AgNPs, as well as the features of the assemblies formed by their association in the presence of anesthetics, were evidenced by transmission electron microscopy images. Atomic force microscopy images showed the characteristics of the films of AgNPs deposited on glass support. The effect of the anesthetics could be described in terms of electrostatic forces between the negatively charged AgNPs and the anesthetic molecules, existing also in their cationic form at the working pH. But also hydrophobic and hydrogen bonding interactions between the coated nanoparticles and anesthetics molecular species should be considered.Keywords: self-assembled nanostructures, UV-vis spectra, TEM, AFM, zeta potential

  14. Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

    Demétrius Fernandes do Nascimento


    Full Text Available To develop and validate a rapid, specific and highly sensitive method to quantify nimodipine in human plasma using dibucaine as the internal standard (IS. The analyte and IS were extracted from plasma samples by liquid-liquid extraction using hexane-ethyl acetate (1:1 v/v. The chromatographic separation was performed on a Varian® Polaris C18 analytical column (3 μm, 50 x 2.0 mm and pre-column SecurityguardTM C18 (4.0 x 3.0 mm with a mobile phase of Acetonitrile-Ammonium acetate 0.02 ml/L (80:20v/v. The method had a chromatographic run time of 4.5 min and linear calibration curve over the range of 0.1- 40 ng/mL (r > 0.9938. The limit of quantification was 100 pg/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. This validated method was successfully applied in determining the pharmacokinetic profile of nimodipine tablets of 30 mg administered to 24 healthy volunteers. The proposed method of analysis provided a sensitive and specific assay for nimodipine determination in human plasma. The time for the determination of one plasma sample was 4.5 min. This method is suitable for the analysis of nimodipine in human plasma samples collected for pharmacokinetic, bioavailability or bioequivalence studies in humans.Um método rápido, específico e sensível para quantificar nimodipino em plasma humano usando dibucaína como padrão interno (IS é descrito. O analito e o IS foram extraídos das amostras de plasma por extração líquido-líquido usando hexano-acetato de etila (1:1 v/v. A separação cromatográfica foi realizada utilizando-se uma coluna analítica C18 Varian® Polaris (3 μm, 50 x 2,0 mm e uma pré-coluna SecurityguardTM C18 (4,0 x 3,0 mm e acetonitrila-acetato de amônia 0,02 mol/L (80:20 v/v como fase móvel. O método apresentou tempo total de corrida de 4,5 min e curva de calibração linear com concentrações entre 0,1-40 ng/mL (r > 0,9938. O limite de quantificação foi de 100