SR 95191, a selective inhibitor of type A monoamine oxidase with dopaminergic properties. I. Psychopharmacological profile in rodents.
SR 95191 [3-(2-morpholino-ethyl-amino)-4-cyano-6-phenyl-pyridazine], a novel compound, has been shown in preliminary experiments to inhibit type A monoamine oxidase (MAO). This report describes the activities of SR 95191 in behavioral experiments in mice and rats and shows that SR 95191 has the profile of a selective type A MAO inhibitor (MAOI). Moreover, SR 95191 also possesses dopamine (DA) stimulant properties. The activities of SR 95191 were compared to those of the MAOIs moclobemide, clorgyline, pargyline and l-deprenyl, as well as to those of the antidepressant drugs imipramine, nomifensine and indalpine and to those of the DAergic drugs (+)-amphetamine and apomorphine. SR 95191 p.o. antagonized the effects of reserpine in mice and rats, decreased immobility in the mouse despair test, antagonized haloperidol-induced catalepsy in rats and potentiated 5-hydroxytryptophan in mice and rats with an overall potency which was half that of imipramine. SR 95191, like moclobemide, did not potentiate yohimbine-induced lethality and did not antagonize oxotremorine-induced tremor. Like selective type A MAOIs, SR 95191 potentiated 5-hydroxytryptophan-induced tremor without affecting beta-phenethylamine-induced stereotypies in mice. SR 95191 did not antagonize 3-hydroxy-4-methyl-alpha-phenylethylamine-induced hyperthermia. Like all DA stimulant drugs, SR 95191 induced stereotypies in rats, which were blocked by haloperidol and alpha-methylparatyrosine, and induced contralateral turning in mice with a unilateral striatal 6-hydroxydopamine lesion. Based on these results, it is postulated that SR 95191 has a unique profile of activity combining the properties of a selective type A MAO inhibitor and those of an atypical DAergic drug.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D003010:Clorgyline / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000037:antagonists & inhibitors; D007099:Imipramine / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D010293:Pargyline / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000037:antagonists & inhibitors; D012642:Selegiline / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects
D000662:Amphetamines; D000928:Antidepressive Agents; D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D011724:Pyridazines; D009627:Nomifensine; C001632:4-methyl-alpha-ethyl-m-tyramine; D012642:Selegiline; D007980:Levodopa; D010095:Oxotremorine; D012110:Reserpine; C051273:SR 95191; D010293:Pargyline; D006916:5-Hydroxytryptophan; D006220:Haloperidol; D003010:Clorgyline; D007099:Imipramine; D020912:Moclobemide; C018181:indalpine