Stimulus-sensitive myoclonus of the baboon Papio papio: pharmacological studies reveal interactions between benzodiazepines and the central cholinergic system.
The baboon Papio papio develops a nonepileptic myoclonus 20 to 30 min after i.m. benzodiazepine injection. It is characterized by bilateral jerks involving mainly the neck and the trunk, by the absence of any correlative EEG paroxysmal discharge, and by its facilitation during movement or agitation. This myoclonus resembles the intention myoclonus of human patients as seen, for example, after anoxia. We found in experiments on 10 adolescent baboons that atropine alone induced the myoclonus for several hours, that physostigmine completely antagonized the benzodiazepine-induced as well as the atropine-induced myoclonus, and that the peripherally acting cholinergic antagonist, methyl-QNB, and agonist prostigmine had no action on the myoclonus, suggesting that the benzodiazepine-induced myoclonus in this species depends on a strong depression of the central cholinergic system by benzodiazepine. The benzodiazepine-induced myoclonus was mediated by benzodiazepine receptors as it was blocked by the specific benzodiazepine receptor antagonist, Ro 15-1788, which did not block atropine-induced myoclonus; latency to myoclonus after benzodiazepine was longer than after atropine. These facts suggest that benzodiazepines, by an as yet unknown mechanism, induce a depression of the cholinergic system which in turn leads to the development of myoclonus. Finally, the benzodiazepine-induced myoclonus of the baboon can be considered as a good model for testing drugs that act on the muscarinic cholinergic system and also for testing benzodiazepine-acetylcholine interactions.
Rektor
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Bryere
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Silva-Barrat
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Menini
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D000818:Animals; D001285:Atropine; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology; D002998:Clonazepam; D004347:Drug Interactions; D005442:Flumazenil; D009207:Myoclonus / Q000139:chemically induced / Q000503:physiopathology*; D009388:Neostigmine / Q000494:pharmacology; D010215:Papio; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000031:analogs & derivatives / Q000494:pharmacology
D001570:Benzodiazepinones; D001569:Benzodiazepines; D009388:Neostigmine; D005442:Flumazenil; D002998:Clonazepam; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D010830:Physostigmine; C054940:clidinium