chlormethiazole

Summary

Summary: A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors.

Top Publications

  1. Hutchinson P, O Connell M, Coles J, Chatfield D, Coleman M, Al Rawi P, et al. Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent. Br J Clin Pharmacol. 2002;53:275-83 pubmed
    ..The objective of the study was to assess the feasibility of administrating a potential neuro-protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury ..
  2. Liu C, Chung J, Seitz H, Russell R, Wang X. Chlormethiazole treatment prevents reduced hepatic vitamin A levels in ethanol-fed rats. Alcohol Clin Exp Res. 2002;26:1703-9 pubmed
    ..This study investigated whether treatment with chlormethiazole, a CYP inhibitor, restores vitamin A in the livers of ethanol-fed rats...
  3. Seifert J, Peters E, Jahn K, Metzner C, Ohlmeier M, te Wildt B, et al. Treatment of alcohol withdrawal: chlormethiazole vs. carbamazepine and the effect on memory performance--a pilot study. Addict Biol. 2004;9:43-51 pubmed
    ..Two different medical strategies [chlormethiazole (CMZ) vs. carbamazepine (CBZ)] in the treatment of inpatients with alcohol withdrawal syndrome were compared...
  4. Baldwin H, Colado M, Murray T, De Souza R, Green A. Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine. Br J Pharmacol. 1993;108:590-6 pubmed
    ..2. Administration of chlormethiazole (50 mg kg-1, i.p...
  5. Baldwin H, Williams J, Snares M, Ferreira T, Cross A, Green A. Attenuation by chlormethiazole administration of the rise in extracellular amino acids following focal ischaemia in the cerebral cortex of the rat. Br J Pharmacol. 1994;112:188-94 pubmed
    ..3. Administration of chlormethiazole (200 mg kg-1, i.p...
  6. Wilby M, Hutchinson P. The pharmacology of chlormethiazole: a potential neuroprotective agent?. CNS Drug Rev. 2004;10:281-94 pubmed
    b>Chlormethiazole is a thiazole derivative with a long history of use as a sedative agent...
  7. Cederbaum A. Role of CYP2E1 in ethanol-induced oxidant stress, fatty liver and hepatotoxicity. Dig Dis. 2010;28:802-11 pubmed publisher
    ..These results show that CYP2E1 plays a major role in ethanol-induced fatty liver and oxidant stress. Restoring CYP2E1 in the CYP2E1 KO mice restores ethanol-induced fatty liver and oxidant stress. ..
  8. Batel P, Lariviere P. [Late-onset alcohol withdrawal syndrome]. Ann Med Interne (Paris). 2000;151 Suppl B:B27-9 pubmed
    ..The first symptoms of AWS appeared only the 4-th day after hospitalization and the patient quickly developed a clinical state of delirium tremens. Delay in the onset of this AWS is discussed...
  9. Holzbach R, Ihlow C, Takla T, Kemper U, Naber D. [Comparison of Two Symptom-Triggered Treatments for Alcohol Withdrawal: HAES vs. SAB-P]. Fortschr Neurol Psychiatr. 2016;84:83-7 pubmed publisher
    ..Simple handling, clomethiazol, oxazepam or diazepam as applicable medication and clear documentation are the advantages of HAES. ..

More Information

Publications95

  1. Chmielewska B, Dudkowska Konopa A, Nowicka Tarach B, Semczuk W, Stelmasiak Z. [Convulsive status epilepticus--clinical analysis of patients treated iin the Neurological Clinics, Medical Academy in Lublin in the years 1986-1995]. Ann Univ Mariae Curie Sklodowska Med. 1998;53:165-71 pubmed
    ..5-2 (6%) to 2-6 or above 6 hrs (46% each) after continuous i.v. administration of BZD or chlormethiazole (53%) when ineffective. No side effects were noted...
  2. Simi A, Porsmyr Palmertz M, Hjertén A, Ingelman Sundberg M, Tindberg N. The neuroprotective agents chlomethiazole and SB203580 inhibit IL-1beta signalling but not its biosynthesis in rat cortical glial cells. J Neurochem. 2002;83:727-37 pubmed
  3. Grässler W. [The pre-delirium syndrome in alcoholic patients in ambulatory care and its treatment]. Psychiatr Neurol Med Psychol (Leipz). 1989;41:99-104 pubmed
    ..30 times Diazepam and Haloperidol effected a cure, while in 61 attacks it appeared that treatment with Chlormethiazol was inevitable. Results are discussed and conclusions drawn...
  4. Addae J, Ali N, Youssef F, Stone T. AMPA receptor activation reduces epileptiform activity in the rat neocortex. Brain Res. 2007;1158:151-7 pubmed
  5. Hepp U. [Diagnosis and treatment of delirium]. Praxis (Bern 1994). 2002;91:455-63 pubmed
    ..Other treatment strategies, especially the use of newer atypical antipsychotic medications are outlined. ..
  6. Elsing C, Stremmel W, Grenda U, Herrmann T. Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit: an open, single-center randomized study. Am J Drug Alcohol Abuse. 2009;35:189-92 pubmed publisher
    ..No serious side effects were detected. GHB effectively controls AWS symptoms in medical ICU patients. The rapid initial treatment response of GHB in contrast to CLO has no influence on duration of patient withdrawal. ..
  7. Wu Y, Nan L, Bardag Gorce F, Li J, French B, Wilson L, et al. The role of laminin-integrin signaling in triggering MB formation. An in vivo and in vitro study. Exp Mol Pathol. 2005;79:1-8 pubmed
    ..The data indicate that laminin-integrin signaling which activates ERK, triggered MB formation in vitro, and an inhibitor of the signaling cascade reduced MB formation. ..
  8. Godecke Koch T, Holze I, Wilhelm Gossling C, Dietrich D, Emrich H. [Clomethiazole as an adjuvant in the treatment of confusional psychosis]. Fortschr Neurol Psychiatr. 2001;69:278-83 pubmed
    ..A brief review about this delirium-like psychosis and current knowledge of therapeutic strategies is presented. We discuss clomethiazole as a possible potential adjunct in the treatment of confusional psychoses. ..
  9. Marshall J, Ridley R. Assessment of cognitive and motor deficits in a marmoset model of stroke. ILAR J. 2003;44:153-60 pubmed
    ..Nevertheless, the long-term nature and consistency of the motor deficits make this model ideal for assessing the worth of restorative therapies. ..
  10. Michaut A, Le Guillou D, Moreau C, Bucher S, McGill M, Martinais S, et al. A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen. Toxicol Appl Pharmacol. 2016;292:40-55 pubmed publisher
    ..In cells pretreated with the CYP2E1 inhibitor chlormethiazole, recovery of ATP was significantly higher in the presence of stearate with low (2...
  11. Green A, Hainsworth A, Misra A, Debens T, Jackson D, Murray T, et al. The interaction of AR-A008055 and its enantiomers with the GABA(A) receptor complex and their sedative, muscle relaxant and anticonvulsant activity. Neuropharmacology. 2001;41:167-74 pubmed
    ..The current data suggest that the proposed GABA uptake inhibitory property of (R)-(+)-AR-A008055 fails to produce significant sedative, myorelaxant or anticonvulsant activity. ..
  12. Bonnet U, Hamzavi Abedi R, Specka M, Wiltfang J, Lieb B, Scherbaum N. An open trial of gabapentin in acute alcohol withdrawal using an oral loading protocol. Alcohol Alcohol. 2010;45:143-5 pubmed publisher
    ..Among them, two developed an epileptic seizure. Oral 800 mg gabapentin (loaded up to 3200 mg in the first 24 h) is helpful only in reducing less severe and less complicated acute AWS. ..
  13. Liu J, Wang L. Gamma aminobutyric acid (GABA) receptor agonists for acute stroke. Cochrane Database Syst Rev. 2013;:CD009622 pubmed publisher
    ..Four trials measured death and dependency at three months in chlormethiazole versus placebo without significant difference (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.95 to 1...
  14. Horstmann E, Conrad E, Daweke H. [Severe course of delirium tremens. Results of treatment and late prognosis]. Med Klin (Munich). 1989;84:569-73 pubmed
    ..Life expectancy was only 9.3 years. Of 29 patients who came for follow-up, 55% showed clinical evidence of alcohol dependency, 65% had elevated gamma-glutamyl-transferase.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  15. Bokström K, Balldin J. A rating scale for assessment of alcohol withdrawal psychopathology (AWIP). Alcohol Clin Exp Res. 1992;16:241-9 pubmed
    ..This new scale, capable of identifying psychopathology and changes over time, may be used alone or together with physiological scales to identify subgroups of patients undergoing withdrawal. ..
  16. Vaishnav A, Lutsep H. GABA agonist: clomethiazole. Curr Med Res Opin. 2002;18 Suppl 2:s5-8 pubmed
    ..However, large randomized placebo controlled trials in Europe, Canada and North America did not show the superiority of clomethiazole over placebo that was seen in animal models. ..
  17. Hales T, Lambert J. Modulation of GABAA and glycine receptors by chlormethiazole. Eur J Pharmacol. 1992;210:239-46 pubmed
    The influence of chlormethiazole, on currents evoked by gamma-aminobutyric acid (GABA) and glycine, was investigated under voltage-clamp conditions, in bovine chromaffin cells and murine spinal neurones, respectively...
  18. Riley N, Li J, Worrall S, Rothnagel J, Swagell C, Van Leeuwen F, et al. The Mallory body as an aggresome: in vitro studies. Exp Mol Pathol. 2002;72:17-23 pubmed
    ..These results support the concept that MBs are aggresomes of CK 8 and CK18 and are a result of inhibition of the ubiquitin-proteasome pathway of protein degradation possibly caused by UBB+1. ..
  19. Wang X, Lu Y, Cederbaum A. Induction of cytochrome P450 2E1 increases hepatotoxicity caused by Fas agonistic Jo2 antibody in mice. Hepatology. 2005;42:400-10 pubmed
    ..Administration of chlormethiazole, an inhibitor of CYP2E1, to the Pyr/Jo2-treated mice caused a significant decrease of alanine ..
  20. Jansson A, Böttiger Y. [Choice of sleeping pills to patients with Parkinson disease]. Lakartidningen. 2007;104:1154-5 pubmed
  21. Zeng T, Zhang C, Zhao N, Guan M, Xiao M, Yang R, et al. Impairment of Akt activity by CYP2E1 mediated oxidative stress is involved in chronic ethanol-induced fatty liver. Redox Biol. 2018;14:295-304 pubmed publisher
    ..of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)-Akt adducts, which was significantly inhibited by chlormethiazole (CMZ), an efficient CYP2E1 inhibitor...
  22. Nelson R, Hainsworth A, Lambert D, Jones J, Murray T, Richards D, et al. Neuroprotective efficacy of AR-A008055, a clomethiazole analogue, in a global model of acute ischaemic stroke and its effect on ischaemia-induced glutamate and GABA efflux in vitro. Neuropharmacology. 2001;41:159-66 pubmed
    ..This action may explain both its effect on glutamate efflux in vitro and its neuroprotective effect in vivo. ..
  23. Centerholt C, Ekblom M, Odergren T, Borgå O, Popescu G, Molz K, et al. Pharmacokinetics and sedative effects in healthy subjects and subjects with impaired liver function after continuous infusion of clomethiazole. Eur J Clin Pharmacol. 2003;59:117-22 pubmed
    ..The reduced clomethiazole clearance in patients with moderate/severe liver impairment seems to call for a reduction of clomethiazole dosage. However, sedation was not observed in this group at the investigated dose level. ..
  24. Usala M, Thompson S, Whiting P, Wafford K. Activity of chlormethiazole at human recombinant GABA(A) and NMDA receptors. Br J Pharmacol. 2003;140:1045-50 pubmed
    1. Investigation into the modulatory effects of chlormethiazole at human recombinant gamma-aminobutyric acid A receptor (GABAA) and N-methyl-d-aspartate (NMDA) receptors was undertaken to gain insight into its mechanism of action and ..
  25. Gage J. The neuropsychologic deterioration seen in the placebo group may have been a result of rigorous exclusion criteria. Anesthesiology. 2003;98:1516; author 1516 pubmed
  26. Clarkson A, Clarkson J, Jackson D, Sammut I. Mitochondrial involvement in transhemispheric diaschisis following hypoxia-ischemia: Clomethiazole-mediated amelioration. Neuroscience. 2007;144:547-61 pubmed
    ..In addition, we have shown that protection afforded by CMZ extends to preservation of mitochondrial function and integrity via anti-inflammatory mediated pathways. ..
  27. Croissant B, Loeber S, Diehl A, Nakovics H, Wagner F, Kiefer F, et al. Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal--a RCT. Pharmacopsychiatry. 2009;42:175-81 pubmed publisher
    ..This is an important question for national health care services, since outpatient therapy is more and more asked for as alternative to inpatient settings. ..
  28. Visser S, Pozarek S, Martinsson S, Forsberg T, Ross S, Gabrielsson J. Rapid and long-lasting tolerance to clomethiazole-induced hypothermia in the rat. Eur J Pharmacol. 2005;512:139-51 pubmed
    ..In conclusion, long-lasting tolerance to clomethiazole-induced hypothermia does not involve GABA(A) or 5-HT(1A) receptor functions. Glutamate via NMDA receptors may be involved in the hypothermic response but not in the tolerance. ..
  29. Bugel S, Tanguay R. Multidimensional chemobehavior analysis of flavonoids and neuroactive compounds in zebrafish. Toxicol Appl Pharmacol. 2018;344:23-34 pubmed publisher
    ..intervention with positive allosteric modulators of the GABAA receptor, alfaxalone and chlormethiazole, ameliorated the hyperactive response to picrotoxin, but not for (S)-equol or kaempferol...
  30. Longo V, Ingelman Sundberg M, Amato G, Salvetti A, Gervasi P. Effect of starvation and chlormethiazole on cytochrome P450s of rat nasal mucosa. Biochem Pharmacol. 2000;59:1425-32 pubmed
    ..A reiterative administration of chlormethiazole, a specific inhibitor of 2E1 in liver, strongly inhibited many CYPs, including 2E1, 1A2, 2G1, and 2A in the ..
  31. Chick J, Nutt D. Substitution therapy for alcoholism: time for a reappraisal?. J Psychopharmacol. 2012;26:205-12 pubmed publisher
    ..For a condition where existing therapies are only effective in a proportion of patients, and which has high morbidity and mortality, the time now seems right for reappraising the use of substitute prescribing for alcohol dependence. ..
  32. Harrison P, Sheridan R, Green A, Tattersall J. Effects of anticonvulsants on soman-induced epileptiform activity in the guinea-pig in vitro hippocampus. Eur J Pharmacol. 2005;518:123-32 pubmed
    ..These data suggest that several compounds, in particular clomethiazole, clozapine, felbamate, topiramate and retigabine, merit further evaluation as possible treatments for organophosphate poisoning. ..
  33. Colado M, O SHEA E, Esteban B, Green A. Studies on the neuroprotective effect of the enantiomers of AR-A008055, a compound structurally related to clomethiazole, on MDMA ("ecstasy")-induced neurodegeneration in rat brain. Psychopharmacology (Berl). 2001;157:82-8 pubmed
    ..Since (S)-(-)-AR-A008055 has a similar pharmacology to clomethiazole, these data suggest that drugs which increase GABAA receptor channel opening are neuroprotective against MDMA-induced damage. ..
  34. Franz M, Dlabal H, Kunz S, Ulferts J, Gruppe H, Gallhofer B. Treatment of alcohol withdrawal: tiapride and carbamazepine versus clomethiazole. A pilot study. Eur Arch Psychiatry Clin Neurosci. 2001;251:185-92 pubmed
    ..Vegetative recovery seems to be faster with TIA+CBZ. Results of this exploratory study have to be confirmed by a controlled double-blind study with severity of AWS as an experimental factor. ..
  35. Lyden P, Shuaib A, Ng K, Levin K, Atkinson R, Rajput A, et al. Clomethiazole Acute Stroke Study in ischemic stroke (CLASS-I): final results. Stroke. 2002;33:122-8 pubmed
    ..The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke. ..
  36. Lutz U, Batra A. [Diagnostics and therapy of alcohol withdrawal syndrome: focus on delirium tremens and withdrawal seizure]. Psychiatr Prax. 2010;37:271-8 pubmed publisher
    ..Furthermore non-pharmacological procedures accompanying delirium tremens and a potential integration of viewing videotapes of delirium tremens in the course of alcohol-specific therapy are discussed...
  37. Bär K, Boettger M, Schulz S, Neubauer R, Jochum T, Voss A, et al. Reduced cardio-respiratory coupling in acute alcohol withdrawal. Drug Alcohol Depend. 2008;98:210-7 pubmed publisher
    ..These data indicate diminished vagal function in acute alcohol withdrawal. Applying the methods described thus allows a sensitive detection of vagal neuropathy in this disease. ..
  38. Bardag Gorce F, Riley N, Nan L, Montgomery R, Li J, French B, et al. The proteasome inhibitor, PS-341, causes cytokeratin aggresome formation. Exp Mol Pathol. 2004;76:9-16 pubmed
    ..At the same time, the cells became dissociated from each other, however. The results simulated MB formation. MBs differ from cytokeratin aggresomes both morphologically and in ultrastructure. ..
  39. Clarkson A, Liu H, Schiborra F, Shaw O, Sammut I, Jackson D, et al. Angiogenesis as a predictive marker of neurological outcome following hypoxia-ischemia. Brain Res. 2007;1171:111-21 pubmed
    ..001). We conclude that angiogenesis can be used as a marker of neurodegeneration/neuroprotection for cerebral HI and is correlated to NOS activity and circulating inflammatory mediators. ..
  40. Visser S, Sällström B, Forsberg T, Peletier L, Gabrielsson J. Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats. J Pharmacol Exp Ther. 2006;317:209-19 pubmed
    ..This multicomponent turnover model was able to quantify the CMZ-induced hypothermia, circadian rhythm in baseline, and rapid onset of a long-lasting tolerance to CMZ in rats. ..
  41. Hess D. NXY-059: a hopeful sign in the treatment of stroke. Stroke. 2006;37:2649-50 pubmed
  42. Gasior M, Witkin J, Goldberg S, Munzar P. Chlormethiazole potentiates the discriminative stimulus effects of methamphetamine in rats. Eur J Pharmacol. 2004;494:183-9 pubmed
    b>Chlormethiazole is a positive modulator of gamma-aminobutyric acid (GABA)(A) receptors used in the treatment of alcohol withdrawal seizures...
  43. McBride W, Khalil N, Elliott P, Armstrong M. Clomethiazole alters immune function within an isolated cardiopulmonary bypass circuit. Anesth Analg. 2004;98:1191 pubmed
  44. He Y, Yang L, Liu Y, Zhang J, Tang J, Su J, et al. Characterization of cardamonin metabolism by P450 in different species via HPLC-ESI-ion trap and UPLC-ESI-quadrupole mass spectrometry. Acta Pharmacol Sin. 2009;30:1462-70 pubmed publisher
    ..Furthermore, our research suggests that guinea pigs could be used in the advanced pharmacokinetic studies of cardamonin in vivo. ..
  45. Riley N, Li J, McPhaul L, Bardag Gorce F, Lue Y, French S. Heat shock proteins are present in mallory bodies (cytokeratin aggresomes) in human liver biopsy specimens. Exp Mol Pathol. 2003;74:168-72 pubmed
    ..Ubiquitin and the hsp's colocalized in all MBs in the diseased liver sections. These results indicate that hsp involvement in MB formation is similar to that seen in aggresome formation in other conformational diseases. ..
  46. Modig J. Indications of chlormethiazole as a protective agent in experimental endotoxemia. Eur Surg Res. 1988;20:195-204 pubmed
    b>Chlormethiazole, which is derived from the thiazole moiety of thiamine, possesses sedative, hypnotic and anticonvulsant properties...
  47. Lange Asschenfeldt C, Muller M, Szegedi A, Anghelescu I, Klawe C, Wetzel H. Symptom-triggered versus standard chlormethiazole treatment of inpatient alcohol withdrawal: clinical implications from a chart analysis. Eur Addict Res. 2003;9:1-7 pubmed
    ..Under symptom-triggered therapy, chlormethiazole (CMZ) treatment duration (4.2 +/- 3.5 vs. 7.5 +/- 3.3 days, Mann-Whitney U test: p = 0...
  48. Balldin J, Berggren U, Engel J, Lindstedt G, Sundkler A, Walinder J. Alpha-2-adrenoceptor sensitivity in early alcohol withdrawal. Biol Psychiatry. 1992;31:712-9 pubmed
    ..In contrast, very short-lasting subsensitivity was found in the alpha-2-adrenoceptors regulating blood pressure. ..
  49. Jochum T, Weissenfels M, Seeck A, Schulz S, Boettger M, Voss A, et al. Endothelial dysfunction during acute alcohol withdrawal syndrome. Drug Alcohol Depend. 2011;119:113-22 pubmed publisher
    ..No major influence of treatment was observed. Future studies need to address the relation of EF to cardiac morbidity during alcohol withdrawal. ..
  50. Colado M, Green A. A study of the mechanism of MDMA ('ecstasy')-induced neurotoxicity of 5-HT neurones using chlormethiazole, dizocilpine and other protective compounds. Br J Pharmacol. 1994;111:131-6 pubmed
    ..selective 5-hydroxytryptamine (5-HT) neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') using chlormethiazole and dizocilpine, both known neuroprotective compounds and also gamma-butyrolactone, ondansetron and ..
  51. Ribbing J, Nyberg J, Caster O, Jonsson E. The lasso--a novel method for predictive covariate model building in nonlinear mixed effects models. J Pharmacokinet Pharmacodyn. 2007;34:485-517 pubmed
    ..g. rare genotype). Run in parallel the lasso could be much faster than SCM. Using cross-validation, the lasso provides a validation of the covariate model and does not require the user to specify a P-value for selection. ..
  52. Liu J, Wang L, Ma X, Ji X. Gamma aminobutyric acid (GABA) receptor agonists for acute stroke. Cochrane Database Syst Rev. 2016;10:CD009622 pubmed
    ..Four trials (N = 2909) measured death and dependency at three months for chlormethiazole versus placebo; pooled results did not find a significant difference (risk ratio (RR) 1...
  53. Nelson R, Green A, Hainsworth A. Electrophysiological actions of gamma-aminobutyric acid and clomethiazole on recombinant GABA(A) receptors. Eur J Pharmacol. 2002;452:255-62 pubmed
    ..8-fold increase in maximal current. Both direct activation and gamma-aminobutyric acid potentiation are likely to contribute to the in vivo profile of clomethiazole. ..
  54. Clarkson A, Liu H, Rahman R, Jackson D, Appleton I, Kerr D. Clomethiazole: mechanisms underlying lasting neuroprotection following hypoxia-ischemia. FASEB J. 2005;19:1036-8 pubmed
    ..We further conclude that under conditions of HI, functional deficits are not restricted to the ipsilateral hemisphere and are due, at least in part, to changes in the activity of NOS and arginase. ..
  55. Nisijima K, Shioda K, Yoshino T, Takano K, Kato S. Diazepam and chlormethiazole attenuate the development of hyperthermia in an animal model of the serotonin syndrome. Neurochem Int. 2003;43:155-64 pubmed
    ..the effectiveness of potent 5-HT(2A) receptor antagonists and GABA-enhancing drugs, including diazepam and chlormethiazole. The rectal temperature of the rats was measured, and the noradrenaline (NA) and 5-HT levels in the anterior ..
  56. Kong R, Butterworth J, Aveling W, Stump D, Harrison M, Hammon J, et al. Clinical trial of the neuroprotectant clomethiazole in coronary artery bypass graft surgery: a randomized controlled trial. Anesthesiology. 2002;97:585-91 pubmed
    ..2 microm. There was no difference between the clomethiazole and placebo group in the postoperative change in neuropsychological test scores. Clomethiazole did not improve cerebral outcome following coronary artery bypass surgery. ..
  57. Nan L, Wu Y, Bardag Gorce F, Li J, French B, Fu A, et al. p62 is involved in the mechanism of Mallory body formation. Exp Mol Pathol. 2004;77:168-75 pubmed
    ..Overexpression of p62 in normal mouse hepatocytes induced MB-like aggresomes that were stained by Ub but not by CK8. The results indicate that p62 is involved in the mechanism of MB formation. ..
  58. Green A, Hainsworth A, Jackson D. GABA potentiation: a logical pharmacological approach for the treatment of acute ischaemic stroke. Neuropharmacology. 2000;39:1483-94 pubmed
    ..The diversity of GABA(A) receptor subtypes and the in vivo efficacy of certain GABA(A) receptor ligands in animal models of stroke suggests that GABAmimetic drugs are an undervalued approach to stroke therapy. ..
  59. Nordén T, Siekmann B, Lundquist S, Malmsten M. Physicochemical characterisation of a drug-containing phospholipid-stabilised o/w emulsion for intravenous administration. Eur J Pharm Sci. 2001;13:393-401 pubmed
    ..Thus, the results underline the importance of characterising drug-lipid interactions for the development of lipid-based formulations. ..
  60. Lucht M, Kuehn K, Armbruster J, Abraham G, Gaensicke M, Barnow S, et al. Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: a controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam. Alcohol Alcohol. 2003;38:168-75 pubmed
    ..A change of medication in this group was necessary only when primarily intoxicated patients had reached the non-intoxicated range. Treatment with tiapride/carbamazepine in alcohol-intoxicated patients proved to be safe. ..
  61. Sareen D. Neuroprotective agents in acute ischemic stroke. J Assoc Physicians India. 2002;50:250-8 pubmed
    ..Furthermore, the mechanisms that underlie the development of focal ischemic injury continue to be discovered, opening new therapeutic perspective for neuroprotection that might clinically be applicable in the future. ..
  62. Dittmar G. [Alcoholic delirium--a potentially life-threatening condition]. Fortschr Med. 1994;112:274-6 pubmed
    ..This, together with improvements in intensive medical care, has reduced the mortality rate to 3 to 8%. Concomitant organic diseases may complicate and prolong the condition. A defective state is a possible outcome...
  63. Harmon D, Coleman E, Marshall C, Lan W, Shorten G. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Anesth Analg. 2003;97:13-8, table of contents pubmed
    ..In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery. ..
  64. Wedekind D, Neumann K, Falkai P, Malchow B, Engel K, Jamrozinski K, et al. S100B and homocysteine in the acute alcohol withdrawal syndrome. Eur Arch Psychiatry Clin Neurosci. 2011;261:133-8 pubmed publisher
    ..S100B could be of relevance in the neurobiology of alcohol withdrawal syndromes. It may be indirectly related to the level of stress level or glutamatergic activity during alcohol withdrawal. ..
  65. Chaulk D, Wells J, Evans S, Jackson D, Corbett D. Long-term effects of clomethiazole in a model of global ischemia. Exp Neurol. 2003;182:476-82 pubmed
    ..These data demonstrate the necessity of utilizing more clinically relevant survival times and carefully monitoring/regulating postischemic temperature when assessing potential neuroprotective compounds. ..
  66. Beninger R, Forsyth J, Van Adel M, Reynolds J, Boegman R, Jhamandas K. Subchronic MK-801 behavioural deficits in rats: partial reversal by the novel nitrate GT 1061. Pharmacol Biochem Behav. 2009;91:495-502 pubmed publisher
    ..GT 1061 (0.1; not 0.0001, 0.001, 0.01, 1.0 mg/kg) further enhanced locomotion; the pro-GABA drug chlormethiazole (0.1, 1.0 mg/kg) had no significant effect. In saline-pretreated rats GT 1061 (0.1; not 0.0001, 0...
  67. Soyka M. [Pharmacotherapy of alcohol dependence]. MMW Fortschr Med. 2008;150 Suppl 2:22-4 pubmed
  68. Carlsson K, Savic R, Hooker A, Karlsson M. Modeling subpopulations with the $MIXTURE subroutine in NONMEM: finding the individual probability of belonging to a subpopulation for the use in model analysis and improved decision making. AAPS J. 2009;11:148-54 pubmed publisher
    ..Individual parameter estimates based on IP(k) should be preferable whenever individual parameter estimates are to be used as study output or for simulations. ..
  69. Gasior M, Ungard J, Witkin J. Chlormethiazole: effectiveness against toxic effects of cocaine in mice. J Pharmacol Exp Ther. 2000;295:153-61 pubmed
    b>Chlormethiazole positively modulates the gamma-aminobutyric acid (GABA)(A) receptor complex and is primarily used to treat certain life-threatening neurological events (e.g., refractory seizures and ethanol withdrawal syndrome)...
  70. Radesäter A, Johansson S, Oberg C, Luthman J. The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1beta-induced neurodegeneration. Neurotox Res. 2003;5:433-42 pubmed
    ..The neuroprotective effects exerted by trolox and MK-801 suggest that free radicals and NMDA receptor-mediated processes are involved in IL-1beta -induced neurodegeneration. ..
  71. Addae J, Ali N, Stone T. Effects of AMPA and clomethiazole on spreading depression cycles in the rat neocortex in vivo. Eur J Pharmacol. 2011;653:41-6 pubmed publisher
  72. Bonnet U, Lensing M, Specka M, Scherbaum N. Comparison of two oral symptom-triggered pharmacological inpatient treatments of acute alcohol withdrawal: clomethiazole vs. clonazepam. Alcohol Alcohol. 2011;46:68-73 pubmed publisher
    ..No withdrawal seizure or delirium occurred. Both score-driven treatments were equally effective, safe and well tolerated in this setting. This is the first study demonstrating the utility of clonazepam in the treatment of AWS syndrome. ..
  73. Nimmerrichter A, Walter H, Gutierrez Lobos K, Lesch O. Double-blind controlled trial of gamma-hydroxybutyrate and clomethiazole in the treatment of alcohol withdrawal. Alcohol Alcohol. 2002;37:67-73 pubmed
    ..The most frequently reported side-effect of GHB was transient vertigo, particularly after the evening double dose. ..
  74. Muschler M, Hillemacher T, Kraus C, Kornhuber J, Bleich S, Frieling H. DNA methylation of the POMC gene promoter is associated with craving in alcohol dependence. J Neural Transm (Vienna). 2010;117:513-9 pubmed publisher
    ..Further studies should more closely investigate the impact of these changes on the several derivatives of the POMC gene. ..
  75. Farooque M, Isaksson J, Jackson D, Olsson Y. Clomethiazole (ZENDRA, CMZ) improves hind limb motor function and reduces neuronal damage after severe spinal cord injury in rat. Acta Neuropathol. 1999;98:22-30 pubmed
    ..4 +/- 2.7% in saline-treated injured animals and to 22.7 +/- 5.4% in CMZ-treated rats. Our results thus show that in this model CMZ improves hind limb motor function and attenuates the morphological damage to the spinal cord. ..
  76. Green A, Murray T, Misra A, Snape M, Jones J, Cross A. The metabolism of clomethiazole in gerbils and the neuroprotective and sedative activity of the metabolites. Br J Pharmacol. 2000;129:95-100 pubmed
    ..These data suggest that the neuroprotective action of clomethiazole results from an action of the parent compound and that NLA-715 contributes to the sedative activity of the drug. British Journal of Pharmacology (2000) 129, 95 - 100 ..
  77. Grocott H. Pharmacologic neuroprotection: the search continues. J Extra Corpor Technol. 2007;39:296-301 pubmed
    ..This review summarizes the past, present, and future of pharmacologic neuroprotection for cardiac surgery. ..
  78. Gallardo Caballero E, Lucena M, Andrade R, Rodrigo L, Pérez Martínez J, García Ruiz E. Severe toxic hepatitis related to chlormethiazole. J Hepatol. 2003;39:1092-3 pubmed
  79. Wahlgren N, Diez Tejedor E, Teitelbaum J, Arboix A, Leys D, Ashwood T, et al. Results in 95 hemorrhagic stroke patients included in CLASS, a controlled trial of clomethiazole versus placebo in acute stroke patients. Stroke. 2000;31:82-5 pubmed
    ..The safety of clomethiazole in hemorrhagic stroke patients will be further evaluated in a prospective study that is under way in North America. ..
  80. Colado M, Camarero J, Mechan A, Sanchez V, Esteban B, Elliott J, et al. A study of the mechanisms involved in the neurotoxic action of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') on dopamine neurones in mouse brain. Br J Pharmacol. 2001;134:1711-23 pubmed
  81. Jochum T, Schulz S, Schein M, Schröder R, Voss A, Bär K. Heart rate turbulence during acute alcohol withdrawal syndrome. Drug Alcohol Depend. 2012;122:253-7 pubmed publisher
    ..Increased sympathetic modulation during withdrawal and clomethiazole treatment is not associated with changes of heart rate turbulence parameters predictive of cardiac death after myocardial infarction. ..
  82. Caspari D, Wappler M, Bellaire W. [Treatment of delirium tremens--a comparison between clomethiazole and clorazepate with reference to effectiveness and rate of side effects]. Psychiatr Prax. 1992;19:23-7 pubmed
    ..So treatment with clorazepate proved to be an alternative to standard therapy with clomethiazol even for severe cases of delirium tremens regarding its wide therapeutical range and the low rate of cardio-pulmonary complications...
  83. Schlösser R, Gesierich T, Wagner G, Bolz M, Grunder G, Dielentheis T, et al. Altered benzodiazepine receptor sensitivity in alcoholism: a study with fMRI and acute lorazepam challenge. Psychiatry Res. 2007;154:241-51 pubmed
    ..Moreover, the results suggest enhanced responsivity to an acute GABAergic challenge in the right cerebellum with disease-related disruption of cerebellar functional integrity. ..
  84. Colado M, Murray T, Green A. 5-HT loss in rat brain following 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine. Br J Pharmacol. 1993;108:583-9 pubmed
    ..on hippocampal and cortical 5-HT terminals in rat brain could be prevented by administration of either chlormethiazole or dizocilpine. 2. Administration of MDMA (20 mg kg-1, i.p...
  85. Marshall J, Green A, Ridley R. Comparison of the neuroprotective effect of clomethiazole, AR-R15896AR and NXY-059 in a primate model of stroke using histological and behavioural measures. Brain Res. 2003;972:119-26 pubmed
    ..The overview of the behavioural effects and these new histological findings suggest that NXY-059 was by far the most effective neuroprotective agent of the three examined. ..
  86. Bardag Gorce F, van Leeuwen F, Nguyen V, French B, Li J, Riley N, et al. The role of the ubiquitin-proteasome pathway in the formation of mallory bodies. Exp Mol Pathol. 2002;73:75-83 pubmed
    ..In conclusion, the results support the concept that Mallory bodies are aggresomes which form as the result of the failure of the ubiquitin-proteasome complex to adequately eliminate cytokeratins destined for proteolysis. ..