Sample records for clemastine

  1. Clemastine Enhances Myelination in the Prefrontal Cortex and Rescues Behavioral Changes in Socially Isolated Mice. (United States)

    Liu, Jia; Dupree, Jeffrey L; Gacias, Mar; Frawley, Rebecca; Sikder, Tamjeed; Naik, Payal; Casaccia, Patrizia


    Altered myelin structure and oligodendrocyte function have been shown to correlate with cognitive and motor dysfunction and deficits in social behavior. We and others have previously demonstrated that social isolation in mice induced behavioral, transcriptional, and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC). However, whether enhancing myelination and oligodendrocyte differentiation could be beneficial in reversing such changes remains unexplored. To test this hypothesis, we orally administered clemastine, an antimuscarinic compound that has been shown to enhance oligodendrocyte differentiation and myelination in vitro, for 2 weeks in adult mice following social isolation. Clemastine successfully reversed social avoidance behavior in mice undergoing prolonged social isolation. Impaired myelination was rescued by oral clemastine treatment, and was associated with enhanced oligodendrocyte progenitor differentiation and epigenetic changes. Clemastine induced higher levels of repressive histone methylation (H3K9me3), a marker for heterochromatin, in oligodendrocytes, but not neurons, of the PFC. This was consistent with the capability of clemastine in elevating H3K9 histone methyltransferases activity in cultured primary mouse oligodendrocytes, an effect that could be antagonized by cotreatment with muscarine. Our data suggest that promoting adult myelination is a potential strategy for reversing depressive-like social behavior. Significance statement: Oligodendrocyte development and myelination are highly dynamic processes influenced by experience and neuronal activity. However, whether enhancing myelination and oligodendrocyte differentiation is beneficial to treat depressive-like behavior has been unexplored. Mice undergoing prolonged social isolation display impaired myelination in the prefrontal cortex. Clemastine, a Food and Drug Administration-approved antimuscarinic compound that has been shown to enhance myelination under

  2. Clemastine rescues behavioral changes and enhances remyelination in the cuprizone mouse model of demyelination. (United States)

    Li, Zhifang; He, Yangtao; Fan, Shuangyi; Sun, Binbin


    Increasing evidence suggests that white matter disorders based on myelin sheath impairment may underlie the neuropathological changes in schizophrenia. But it is unknown whether enhancing remyelination is a beneficial approach to schizophrenia. To investigate this hypothesis, we used clemastine, an FDA-approved drug with high potency in promoting oligodendroglial differentiation and myelination, on a cuprizone-induced mouse model of demyelination. The mice exposed to cuprizone (0.2% in chow) for 6 weeks displayed schizophrenia-like behavioral changes, including decreased exploration of the center in the open field test and increased entries into the arms of the Y-maze, as well as evident demyelination in the cortex and corpus callosum. Clemastine treatment was initiated upon cuprizone withdrawal at 10 mg/kg per day for 3 weeks. As expected, myelin repair was greatly enhanced in the demyelinated regions with increased mature oligodendrocytes (APC-positive) and myelin basic protein. More importantly, the clemastine treatment rescued the schizophrenia-like behavioral changes in the open field test and the Y-maze compared to vehicle, suggesting a beneficial effect via promoting myelin repair. Our findings indicate that enhancing remyelination may be a potential therapy for schizophrenia.

  3. Clemastine Potentiates the Human P2X7 Receptor by Sensitizing It to Lower ATP Concentrations*


    Nörenberg, Wolfgang; Hempel, Christoph; Urban, Nicole; Sobottka, Helga; Illes, Peter; Schaefer, Michael


    P2X7 receptors have emerged as potential drug targets for the treatment of medical conditions such as e.g. rheumatoid arthritis and neuropathic pain. To assess the impact of pharmaceuticals on P2X7, we screened a compound library comprising approved or clinically tested drugs and identified several compounds that augment the ATP-triggered P2X7 activity in a stably transfected HEK293 cell line. Of these, clemastine markedly sensitized Ca2+ entry through P2X7 to lower ATP concentrations. Extrac...

  4. Dual CD system-modified MEEKC method for the determination of clemastine and its impurities. (United States)

    Orlandini, Serena; Giannini, Iacopo; Navarro, Mercedes Villar; Pinzauti, Sergio; Furlanetto, Sandra


    A dual system of CDs was used for the first time in MEEKC with the aim of determining clemastine and its three main related impurities in both drug substances and tablets. The addition of methyl-β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin to the microemulsion pseudo-stationary phase was essential to increase the resolving power of the system to obtain a baseline separation among the compounds. The best microemulsion composition was identified by mixture design and the effects of the factors concentrations of CDs and voltage were investigated by a response surface study applying a Central Composite Design. In both cases, Derringer's desirability function made it possible to find the global optimum, which corresponded to the following combination: microemulsion, 89.8% 10 mM borate buffer pH 9.2, 1.5% n-heptane and 8.7% of SDS/n-butanol in 1:2 ratio; 18 mM methyl-β-cyclodextrin, 38 mM heptakis(2,6-di-O-methyl)-β-cyclodextrin, 17 kV. By applying these conditions, the separation was completed in about 5.5 min. The method was validated following International Conference on Harmonisation guidelines and was applied to a real sample of clemastine tablets.

  5. The antihistamines clemastine and desloratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines. (United States)

    Döbbeling, Udo; Waeckerle-Men, Ying; Zabel, Franziska; Graf, Nicole; Kündig, Thomas M; Johansen, Pål


    Mycosis fungoides and its leukaemic counterpart Sézary syndrome are the most frequent cutaneous T-cell lymphomas (CTCL), and there is no cure for these diseases. We evaluated the effect of clinically approved antihistamines on the growth of CTCL cell lines. CTCL cell lines as well as blood lymphocytes from patients with Sézary syndrome were cultured with antihistamines, and the cell were analysed for proliferation, apoptosis and expression of programmed death molecules and transcription factors. The two antihistamines clemastine and desloratadine, currently used for symptom alleviation in allergy, induced potent reduction of the activities of the constitutively active transcription factors c-Myc, STAT3, STAT5a and STAT5b in mycosis fungoides and Sézary syndrome cell lines. This inhibition was followed by apoptosis and cell death, especially in the Sézary syndrome-derived cell line Hut78 that also showed increased expression of the programmed death-1 (PD-1) after clemastine treatment. In lymphocytes isolated from Sézary syndrome patients, the CD4-positive fraction underwent apoptosis after clemastine treatment, while CD4-negative lymphocytes were little affected. Because both c-Myc and STAT transcription factors are highly expressed in proliferating tumours, their inhibition by clemastine, desloratadine and other inhibitors could complement established chemotherapies not only for cutaneous T-cell lymphomas but perhaps also other cancers.

  6. HPLC determination of related substances in clemastine fumarate and its tablets*%HPLC法测定富马酸氯马斯汀及富马酸氯马斯汀片的有关物质

    Institute of Scientific and Technical Information of China (English)

    刘德胜; 徐玉文; 李玉梅


    Objective:High performance liquid chromatography method was established to determine the related substances and the degradation substances in clemastine fumarate ant its tablets. Methods:An ODS -3 C18 column (250 mm x4. 6 mm,5 μm)with UV detection at 210 nm,and acetonitrile -sodium octanesulfonate solution (50:50) as the mobile phase were used in HPLC. The flow rate was 1. 0 mL·min-1 ,and the temperature of the column was 35 t. Results; An excellent separation was achieved for clemastine fumarate, excipient and its related substances. The reproducibility and precision of the method were good( RSD <0. 3% ). Conclusion:This method was accurate, simple, quick and effective for determination of related substances and the degradation substances in clemastine fumarate tablets. It was also suitable for the quality control for clemastine fumarate and its tablets.%目的:采用高效液相色谱法测定富马酸氯马斯汀及片剂中的有关物质和降解产物.方法:采用ODS -3 C18色谱柱(250mm ×4.6 mm,5μm);柱温为35℃;流动相为乙腈-辛烷磺酸钠溶液(50∶50);流速为1.0 mL·min-1;检测波长为210 nm;进样量为10μL.结果:各降解产物、辅料均可与富马酸氯马斯汀主峰良好分离,方法的精密度和重复性良好(RSD<0.3%).结论:经方法学验证,该法灵敏、准确,适用于富马酸氯马斯汀及片剂中有关物质的测定.

  7. Determination by HPLC-MS-MS method and bioequivalence of clemastine in health volunteers%酚麻氯汀胶囊中氯马斯汀的LC-MS-MS测定方法及在健康人体中的相对生物利用度研究

    Institute of Scientific and Technical Information of China (English)

    宋冬梅; 张煊; 刘婷立; 郭智; 易志恒; 潘琳


    目的:建立人血浆中氯马斯汀的LC-MS-MS测定法,评价酚麻氯汀胶囊中氯马斯汀在健康人体的相对生物利用度.方法:采用开放、随机、双周期、两制剂、双序列单次给药的交叉试验设计.19例健康志愿者分别口服相当于富马酸氯马斯汀0.67 mg剂量的受试制剂和参比制剂.以硝苯地平为内标,采用甲基叔丁基醚为提取溶剂,用LC-MS-MS法测定血浆中氯马斯汀的质量浓度,经WinNonlin 6.0软件处理血药质量浓度数据后得药动学数据.结果:氯马斯汀的线性范围为5.09~407.20 ng·L-1,定量下限为5.09ng·L-1,绝对回收率为79.7%~80.6%,绝对基质效应为101.0%~103.6%,批内和批间精密度与准确度均符合要求.受试制剂中氯马斯汀的t1/2为(20.67±3.56)h,Cmax为(142.07±65.69)ng·L-1,Tmax为(4.21±1.23)h,AUC0-t为(2 829±1 681)ng·h·L-1;参比制剂中氯马斯汀的的t1/2为(20.83±4.94)h,Cmax为(1 46.55±60.16)ng·L-1,Tmax为(4.13±1.27)h,AUC0-t为(2 839±1 560)ng·h·L-1.以AUC0-t计算,与参比制剂比较,受试制剂中氯马斯汀的平均相对生物利用度为(101.7±23.4)%.结论:本方法灵敏、准确,适于临床药动学研究;两种制剂中的氯马斯汀具有生物等效性.%Objective: To develop an HPLC-MS-MS assay for determination of clemastine in human plasma , and estimate the bioequivalence of clemastine in paracetamol, clemastine fumarate and pseudoephedrine hydro-chloride capsule in healthy volunteers. Methods; An open, randomized, two-periods, two-treatment, two-sequence, and crossover clinical trial was performed in 19 healthy male volunteers. They were orally administrated with a single dose of clemastine fumarate 0. 67 mg. The plasma concentration of clemastine was determined by LC-MS-MS using nifedipine as an internal standard and methyl tert-butyl ether as an extraction solvent. The plasma concentration-time curves as well as pharmacokinetics of both test and reference formulations were analyzed

  8. 复方氯马斯汀霜制备和治疗季节性面部接触性皮炎的临床疗效%Preparation of compound clemastine cream and its clinical efficacy for the treatment of seasonal contact dermatitis in the face

    Institute of Scientific and Technical Information of China (English)

    黄贤琦; 李冠勇; 张华


    目的:观察自制复方氯马斯汀霜治疗季节性面部接触性皮炎的临床疗效。方法:霜剂的制备采用o/w法。将94名门诊和住院患者随机分成两组,治疗组(51例)用复方氯马斯汀霜,对照组(43例)用康夫丽乐软膏,比较两组的疗效。结果:复方氯马斯汀霜组的治愈率和总有效率显著高于对照组(P<0.01,P<0.05)。结论:该制剂疗效确切,不良反应少,是治疗季节性面部接触性皮炎的理想药物,值得临床推广。%OBJECTIVE:To prepare compound clemastine cream(COC)and to evaluate its clinical efficacy for the treatment of seasonal contact dermatitis in the face.METHODS:The preparation was obtained by traditional o/w method.94 outpatients and inpatients were randomly divided into active group(COC group)and control group(Kangfulire ointment group).RESULTS:The healing rate and the total efficient rate were significantly higher than those of control group(p<0.01,p<0.05).CONCLUSION:COC has reliable clinical efficacy and has little side effects,so it is one of the specific preparations for the treatment of contact dermatitis and it can be widely used in the clinics.

  9. Kinetic aspects of hollow fiber liquid-phase microextraction and electromembrane extraction

    DEFF Research Database (Denmark)

    Gjelstad, Astrid; Jensen, Henrik; Rasmussen, Knut Einar


    In this paper, extraction kinetics was investigated experimentally and theoretically in hollow fiber liquid-phase microextraction (HF-LPME) and electromembrane extraction (EME) with the basic drugs droperidol, haloperidol, nortriptyline, clomipramine, and clemastine as model analytes. In HF...

  10. Drug: D00666 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available histaminic Therapeutic category: 4419 ATC code: D04AA14 R06AA04 H1-receptor antagon...D00666 Drug Clemastine fumarate (JP16/USP); Tavist (TN) C21H26ClNO. C4H4O4 459.1813 459.9624 D00666.gif Anti

  11. Drug: D03535 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04A ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04AA Antihistamines for topical use D04AA14 Cl...(USAN) USP drug classification [BR:br08302] Respiratory Tract/Pulmonary Agents Antihistamines Clemastine D03

  12. Circulating histamine and neutrophil chemotactic activity during allergen-induced asthma: the effect of inhaled antihistamines and anti-allergic compounds. (United States)

    Morgan, D J; Moodley, I; Cundell, D R; Sheinman, B D; Smart, W; Davies, R J


    Plasma histamine and serum neutrophil chemotactic activity (S-NCA) were measured in ten atopic asthmatic patients on four separate occasions after allergen bronchial provocation testing (BPT). Single doses of inhaled sodium cromoglycate (SCG; 20 mg), clemastine (0.5 mg), ketotifen (0.5 mg) and isotonic saline (0.9% NaCl) placebo were administered 30 min before bronchial provocation testing in random order and double-blind. The airflow obstruction after BPT was monitored by measurement of forced expiratory volume in 1 s (FEV1). Plasma histamine was measured by the double-isotope radioenzymatic assay and S-NCA by a modified Boyden chamber technique. A highly significant decrease in FEV1 after BPT occurred on the placebo pre-treatment visit (P less than 0.001). Prior administration of inhaled SCG, clemastine and ketotifen significantly reduced the decrease in airflow obstruction seen after BPT when compared with placebo treatment (P less than 0.01, P less than 0.02, P less than 0.05 respectively). No significant alteration in plasma histamine was detected during allergen-induced airflow obstruction. Levels of S-NCA were significantly higher 5, 10 and 15 min after BPT when compared with the pre-challenge level (P less than 0.01, P less than 0.01, P less than 0.001 respectively). These levels were not significantly decreased when airflow obstruction was inhibited by the prior inhalation of SCG, clemastine or ketotifen.

  13. Itch and skin rash from chocolate during fluoxetine and sertraline treatment: Case report

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    Svenson Svante


    Full Text Available Abstract Background The skin contains a system for producing serotonin as well as serotonin receptors. Serotonin can also cause pruritus when injected into the skin. SSRI-drugs increase serotonin concentrations and are known to have pruritus and other dermal side effects. Case presentation A 46-year-old man consulted his doctor due to symptoms of depression. He did not suffer from any allergy but drinking red wine caused vasomotor rhinitis. Antidepressive treatment with fluoxetine 20 mg daily was initiated which was successful. After three weeks of treatment an itching rash appeared. An adverse drug reaction (ADR induced by fluoxetine was suspected and fluoxetine treatment was discontinued. The symptoms disappeared with clemastine and betametasone treatment. Since the depressive symptoms returned sertraline medication was initiated. After approximately two weeks of sertraline treatment he noted an intense itching sensation in his scalp after eating a piece of chocolate cake. The itch spread to the arms, abdomen and legs and the patient treated himself with clemastine and the itch disappeared. He now realised that he had eaten a chocolate cake before this episode and remembered that before the first episode he had had a chocolate mousse dessert. He had never had any reaction from eating chocolate before and therefore reported this observation to his doctor. Conclusions This case report suggests that there may be individuals that are very sensitive to increases in serotonin concentrations. Dermal side reactions to SSRI-drugs in these patients may be due to high activity in the serotonergic system at the dermal and epidermo-dermal junctional area rather than a hypersensitivity to the drug molecule itself.

  14. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

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    Joseph D Planer


    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  15. Serotonin Syndrome after Sertraline Overdose in a Child: A Case Report

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    Joana Grenha


    Full Text Available Serotonin syndrome is a potentially life-threatening drug effect. It may be misdiagnosed because it has mostly been reported in adults. Case Report. An 8-year-old girl with behavioral problems and medicated with risperidone and sertraline was admitted in the emergency department after she had taken voluntarily 1500 mg of sertraline (50 mg/kg. At admission, she had marked agitation, visual hallucinations, diaphoresis, flushing, and tremor. She had fever and periods of hypertension. She also showed generalized rigidity and involuntary movements. She was treated with fluids and iv diazepam, midazolam, clemastine, and biperiden. As the patient presented a severe insomnia and a progressive rhabdomyolysis, she was transferred to pediatric intensive care unit (ICU, where she was under treatment with cyproheptadine, mechanical ventilation, and muscular paralysis for 11 days. She was discharged from hospital a few days later with no neurological sequelae. Conclusions. Serotonin syndrome is still not well recognized by physicians. In our patient, the diagnosis was made early due to the history of overdose with serotonin reuptake inhibitors and the triad of mental, neurological, and autonomic signs. Parents must be educated to prevent children from having free access to drugs, avoiding self-medication or overdose.

  16. Utility of 4-chloro-7-nitrobenzofurazan (NBD-CI) for the Spectrophotometric and spectrofluorometric determination of several antihistamine and antihypertensive drugs. (United States)

    Abd, El-Hay Soad S; Colyer, Christa L; Hassan, Wafaa S; Shalaby, Abdalla


    New, sensitive, and selective spectrophotometric and spectrofluorometric methods have been developed for determination of clemastine hydrogen fumarate (Clem), loratadine (Lor), losartan potassium (Los), and ramipril (Ram) in both pure form and pharmaceutical formulations using 4-chloro-7-nitrobenzofurazan (NBD-CI), which is a highly sensitive chromogenic and fluorogenic reagent. The relation between absorbance at 470, 467, 471, and 469 nm and the concentration was linear over the ranges 5-35, 10-100, 10-90, and 10-120 microg/mL for Clem, Lor, Los, and Ram, respectively. The complexation products were also measured spectrofluorometrically at the emission wavelength 535 nm for Clem, Lor, and Ram and at 538 nm for Los with excitation at 477 and 452 nm for Clem and Lor, respectively, and 460 nm for both Los and Ram. The fluorescence intensity was directly proportional to the drug concentration over the ranges 0.05-0.5, 5-20, 1-6, and 2-15 microg/mL for Clem, Lor, Los, and Ram, respectively. The methods were successfully applied for the determination of the studied drugs in pharmaceutical dosage forms with excellent recovery.

  17. Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations (United States)

    Hassan, Wafaa S.; El-Henawee, Magda M.; Gouda, Ayman A.


    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of three histamine H1-antagonists drugs, e.g., chlorphenoxamine hydrochloride (CPX), diphenhydramine hydrochloride (DPH) and clemastine (CMT) in bulk and in their pharmaceutical formulations. The first method depend upon the reaction of molybdenum(V) thiocyanate ions (Method A) with the cited drugs to form stable ion-pair complexes which extractable with methylene chloride, the orange red color complex was determined colorimetrically at λmax 470 nm. The second method is based on the formation of an ion-association complex with alizarin red S as chromogenic reagents in acidic medium (Method B), which is extracted into chloroform. The complexes have a maximum absorbance at 425 and 426 nm for (DPH or CMT) and CPX, respectively. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration ranges of 5.0-40 and 5-70 μg mL -1 for molybdenum(V) thiocyanate (Method A) and alizarin red S (Method B), respectively. For more accurate analysis, Ringbom optimum concentration ranges were calculated. The molar absorptivity, Sandell sensitivity, detection and quantification limits were calculated. Applications of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the procedure was confirmed by applying the standard addition technique and the results obtained in good agreement well with those obtained by the official method.

  18. Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish

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    David Zada


    Full Text Available Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS, a psychomotor retardation associated with mutations in the thyroid-hormone (TH transporter MCT8 (monocarboxylate transporter 8. AHDS is characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand the mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8−/− zebrafish model. The quantification of genetic markers for oligodendrocyte progenitor cells (OPCs and mature oligodendrocytes revealed reduced differentiation of OPCs into oligodendrocytes in mct8−/− larvae and adults. Live imaging of single glial cells showed that the number of oligodendrocytes and the length of their extensions are reduced, and the number of peripheral Schwann cells is increased, in mct8−/− larvae compared with wild type. Pharmacological analysis showed that TH analogs and clemastine partially rescued the hypomyelination in the CNS of mct8−/− larvae. Intriguingly, triiodothyronine (T3 treatment rescued hypomyelination in mct8−/− embryos before the maturation of the blood–brain barrier (BBB, but did not affect hypomyelination in older larvae. Thus, we expressed Mct8-tagRFP in the endothelial cells of the vascular system and showed that even relatively weak mosaic expression completely rescued hypomyelination in mct8−/− larvae. These results suggest potential pharmacological treatments and BBB-targeted gene therapy that can enhance myelination in AHDS and possibly in other TH-dependent brain disorders.

  19. The effect of betahistine on vestibular habituation: comparison of rotatory and sway habituation training. (United States)

    Mierzwinski, J; Kazmierczak, H; Pawlak-Osinska, K; Piziewicz, A


    This study was designed to investigate the effect of histaminergic agonists and antagonists on the acquisition of vestibular habituation. The experimental animals, pigeons, were subjected to unilateral rotatory and sway habituation training sessions. The habituation of postural reflexes and post-rotatory head nystagmus was assessed. Vestibular habituation in the control group was achieved by adopting the kinetic reflex posture after approximately 9 training sessions, and after 10 and 14 training sessions, respectively for 50% reduction of the total number of beats (TNB) and the duration of post-rotatory head nystagmus. In the sway adaptation test control pigeons needed nearly 15 training sessions while pigeons receiving betahistine adapted after approximately 8 sessions. Administration of histamine and, most notably, betahistine accelerated the process, while both H1 and H2 antagonists (clemastine, cimetidine) tended to retard it, indicating a less significant contribution of H2 receptors. The cholinergic agent physostigmine strongly retarded habituation while the anticholinergic agent scopolamine markedly accelerated it. In addition the adrenomimetic agent ephedrine also accelerated habituation while the adrenolytic agent droperidol retarded reduction of nystagmus beats. The results indicate that histaminergic receptors play a significant role in the vestibular habituation mechanism but are intricately involved with other types of receptors. Betahistine is clearly the agent of choice for attenuating vestibular effects.

  20. Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry. (United States)

    Hasegawa, Chika; Kumazawa, Takeshi; Lee, Xiao-Pen; Fujishiro, Masaya; Kuriki, Ayako; Marumo, Akemi; Seno, Hiroshi; Sato, Keizo


    Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with 0.4 mL of distilled water and 25 microL of a 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. The eluate was injected into a gas chromatography (GC) injector without evaporation and reconstitution steps, and was detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of the ten drugs from each other and from impurities was generally satisfactory using a DB-1MS column (30 m x 0.32 mm i.d., film thickness 0.25 microm). The recoveries of the ten antihistamines spiked into plasma were 73.8-105%. The regression equations for the ten antihistamines showed excellent linearity with detection limits of 0.02-5.0 ng/0.1 mL. The within-day and day-to-day coefficients of variation for plasma were not greater than 9.9%. The data obtained from determination of diphenhydramine and chlorpheniramine in human plasma after oral administration of the drugs are also presented.

  1. LC-MS/MS法测定人血浆中苯海拉明血药浓度及其制剂的生物等效性研究%Determination of Diphenhydramine in Human Plasma by LC-MS/MS and Bioequivalence Study of Its Preparation

    Institute of Scientific and Technical Information of China (English)

    刘世军; 曹若明; 崔晞; 孙克明; 刘宪勇; 张敏; 郑慧敏


    OBJECTIVE: To develop a method for the determination of diphenhydramine in human plasma, and to study bioequivalence of its preparation in healthy volunteers. METHODS: After blood sample processing, LC-MS/MS method was used. The determination was performed on Inertsil Hilic column (150 mm×3.0 mm,5 μm) with mobile phase consisted of acetonitrile-wa-ter (10 mmol/L ammonium acetate)-formic acid (40:60:1, V|V|V). ESI was applied and operated in positive ion mode: mlz 256→ 167 for diphenhydramine and mlz 344→215 for clemastine (IS) under multiple reaction monitoring (MRM) mode. RESULTS: The linear ranges of diphenhydramine were 0.5-125 ng/ml (r=0.996 5); RSDs of intra-day and inter-day were less than 8% , and method recoveries were 99.4%-103.4% and extraction recoveries were 71.9%-75.3%. Main pharmacokinetic parameters of test preparation and reference preparation after oral administration were as follows: t1/2were(9.892 ± 1.615) h and (10.745 ± 3.227)h; tmax were (2.00 ± 0.81) h and (1.78 ± 0.55)h; cmax were (90.4 ± 20.6)h and (103.0 ± 30.1) h; AUC0-36 h were (806.293 ± 211.453) h and (827.856 ± 223.996)h. CONCLUSIONS: The method is sensitive and accurate, which is suitable for the determination of plasma concentration and bioequiavailability study of diphenhydramine. Two preparations are bioequivalent.%目的:建立测定人血浆中苯海拉明血药浓度的方法,并进行其生物等效性研究.方法:血样经处理后,采用高效液相色谱串联质谱电喷雾(LC-MS/MS)法进样测定.色谱柱为Intersil Hilic(150 mm×3.0mm,5 μm),流动相为乙腈-水(10 mmol/L乙酸铵)-甲酸(40:60:1,V/V/V);电喷雾电离(ESI)离子源,正离子模式,多级反应监测(MRM)方式检测,离子对分别为m/z 256→167(苯海拉明)、m/z 344→215(氯马斯汀,内标).结果:苯海拉明血药浓度在0.5~125 ng/ml范围内线性关系良好(r=0.996 5);日内、日间RSD均<8%,方法回收率为99.4%~103.4%,提取回收率为71.9%~75