The anti-conflict effect of cyproheptadine is not mediated by its 5-hydroxytryptamine antagonistic property.

Cyproheptadine, a 5HT2 receptor antagonist with prominent antimuscarinic and anti-histaminic properties, was shown to have an anti-conflict effect in rats using a modified Geller-Seifter test and also enhanced extinction of conflict behaviour. The selective 5HT2 receptor antagonist ritanserin, however, had neither an anti-conflict effect nor an effect on extinction of conflict behaviour. The muscarinic receptor antagonist scopolamine, on the other hand, was active in both paradigms. The effect of cyproheptadine on extinction of conflict behaviour was decreased by co-administration of physostigmine, an acetylcholinesterase inhibitor, but not affected by the concomitant administration of the muscarine receptor agonist oxotremorine. The results suggest that the anti-conflict effect of cyproheptadine has to be ascribed to its anti-muscarinic activity and is not due to its 5HT2 antagonism.