Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0231530 (twitching)
 2,043 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five members of a novel series of quinoline derivatives which all have similar activities on benzodiazepine receptor binding in vitro were compared in a food-motivated conflict and stress-induced ultrasounds models of anxiety and on suprahyoid muscle twitching in urethane-anaesthetised rats. RU 42382, RU 43028 and RU 39419 showed anxiolytic activity in both tests and RU 40410 was an antagonist. RU 40744 inhibited stress-induced ultrasounds but had little activity in the conflict test. Amphetamine-induced suprahyoid muscle twitching was only weakly inhibited by RU 42382 and RU 43028 in comparison with a classical benzodiazepine agonist. Ro15-1788 antagonised RU 42382 indicating that a major component of its action was agonism at benzodiazepine receptors. RU 39419 had no effect, RU 40744 tended to increase and RU 40410 evoked a small but statistically significant increase in twitching. The same rank order was observed in antagonism of a benzodiazepine in the muscle twitching model. RU 42382 was least effective as an antagonist and RU 40410 most effective. RU 39419 had no effect alone but antagonised the decrease of firing rate of cerebellar Purkinje cells induced by a benzodiazepine in urethane-anaesthetised rats. Comparison of in vivo occupancy of benzodiazepine receptors and efficacy in the conflict test in rats suggests a ranking of agonist intrinsic activity: RU 42382 greater than RU 43028 greater than RU 39419. A simple relationship between intrinsic activity at benzodiazepine receptors and structure of the compounds is proposed.
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PMID:Agonist and antagonist activities at benzodiazepine receptors of a novel series of quinoline derivatives. 282 81

Amphetamine-induced twitching of the suprahyoid muscle in nialamide-pretreated, urethane-anaesthetised rats was inhibited by the benzodiazepine agonists RU 32007, diazepam and chlordiazepoxide and the GABAA agonist muscimol. Ro15-1788 and CGS 8216 induced slight, or no reduction in twitching, respectively, but reversed the effect of RU 32007 and diazepam. Ro15-1788 did not reverse the effect of muscimol. Picrotoxin reversed both muscimol and RU 32007 effects at a dose which induced only a small increase in twitching alone. Higher doses of picrotoxin markedly increased amphetamine twitching and induced twitching in the absence of amphetamine. Ethyl-beta-carboline-3-carboxylate (BCE) weakly increased twitching and reversed the effect of RU 32007. CL 218872 weakly reduced twitching but also weakly antagonised RU 32007. In rats pretreated with a higher dose of nialamide methyl beta-carboline-3-carboxylate (BCM) and BCE induced twitching. BCE-induced twitching was antagonised by RU 32007, Ro15-1788, CGS 8216, muscimol and weakly by CL 218872. Thus, benzodiazepine agonists inhibit twitching and inverse agonists induce twitching, both being blocked by antagonists. Partial agonism (CL 218872) or partial inverse agonism (CGS 8216) may be detected by differential effects against different inducers of twitching.
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PMID:Actions and interactions of benzodiazepine agonists, antagonists and inverse agonists on suprahyoid muscle twitching. 299 66