Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tremorogenic properties of a series of benzylimidoylurea derivatives are described. The most potent member, N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954), produces a reproducible, dose-dependent rest tremor in the mouse with oral doses of 5-100 mg/kg which is also seen in other species (rat, cat, dog, rabbit). The tremor is of constant frequency, rapid onset and short duration. It is not accompanied by akinesia, muscle ridigity, antinociceptive activity, parasympathomimetic effects or marked hypothermia and in these respects differs from tremor produced by oxotremorine. Pretreatment with a microsomal enzyme inhibitor had no effect on the tremor. An LD50 of 165 mg/kg p.o. was calculated in the mouse. After repeated administration both acute and chronic tolerance developed to the tremorogenic effects of LON-954. Evidence for a central site of action is presented, since the tremor could be reproduced following injection of small quantities (50-100 microgram) into the cerebral ventricles of the mouse. Furthermore, the use of spinal, decorticate and and decerebrate rats indicated that although tremor is not of cortical origin, it arises in an area rostral to the inferior colliculi. The mechanism underlying the tremor appears to involve dopaminergic pathways, since the action of LON-954 was antagonised by L-dopa and apomorphine and potentiated by pimozide. Atropine and carbachol were without effect. It is suggested that LON-954 could be used as an alternative to oxotremorine for the detection of anti-Parkinson drugs, particularly those exerting their effects through dopaminergic mechanisms.
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PMID:The pharmacology of N-carbamoyl-2-(2,6-dichlorophenyl)acetamidine hydrochloride (LON-954) a new tremorogenic agent. 58 44

The effect of N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954) on alpha 2-adrenoceptors was studied in in vivo and in vitro preparations. Like yohimbine, LON-954 antagonised the clonidine-induced inhibition of twitch responses in the Auerbach's plexus of guinea pig ileum and rat vas deferens preparations. It also reversed the anti-convulsant effect of clonidine on pentylenetetrazol (PTZ)-induced convulsions in the rat, a property shared by yohimbine. However LON-954 failed to prevent the hypothermic response to clonidine in mice. The dissimilarity in action of LON-954 and yohimbine on clonidine-induced hypothermia could be due to the fact that the anticlonidine effect of yohimbine on hypothermia is mediated through its antiserotonin action. The results indicate that LON-954 acts as an alpha 2-antagonist both centrally and peripherally.
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PMID:Alpha 2-antagonistic effect of N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954). 289 16