SR 95191, a selective inhibitor of type A monoamine oxidase with dopaminergic properties. I. Psychopharmacological profile in rodents.

Abstract

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.

• Authors: P Worms, J P Kan, C G Wermuth, R Roncucci, K Bizière
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 240 Issue 1 Pg. 241-50 (Jan 1987) ISSN: 0022-3565 [Print] United States
• PMID: 3100770 (Publication Type: Journal Article)

Chemical References

• Amphetamines
• Antidepressive Agents
• Benzamides
• Monoamine Oxidase Inhibitors
• Piperidines
• Pyridazines
• Nomifensine
• 4-methyl-alpha-ethyl-m-tyramine
• Selegiline
• Levodopa
• Oxotremorine
• Reserpine
• SR 95191
• Pargyline
• 5-Hydroxytryptophan
• Haloperidol
• Clorgyline
• Imipramine
• Moclobemide
• indalpine

Topics

• 5-Hydroxytryptophan (pharmacology)
• Amphetamines (pharmacology)
• Animals
• Antidepressive Agents (pharmacology)
• Behavior, Animal (drug effects)
• Benzamides (pharmacology)
• Body Temperature (drug effects)
• Catalepsy (chemically induced)
• Clorgyline (pharmacology)
• Drug Interactions
• Female
• Haloperidol (antagonists & inhibitors)
• Imipramine (pharmacology)
• Levodopa (pharmacology)
• Male
• Mice
• Moclobemide
• Monoamine Oxidase Inhibitors (pharmacology)
• Motor Activity (drug effects)
• Nomifensine (pharmacology)
• Oxotremorine (antagonists & inhibitors)
• Pargyline (pharmacology)
• Piperidines (pharmacology)
• Pyridazines (pharmacology)
• Rats
• Rats, Inbred Strains
• Reserpine (antagonists & inhibitors)
• Selegiline (pharmacology)
• Stereotyped Behavior (drug effects)