The involvement of noradrenaline, 5-hydroxytryptamine and acetylcholine in imipramine-induced seizures in mice.

The influence of some noradrenergic, 5-hydroxytryptaminergic and cholinergic agents on imipramine-induced seizures were investigated in mice. DL-threo-3,4-dihydroxyphenylserine (DOPS) and pargyline significantly potentiated imipramine-induced seizures. Phentolamine and prazosin significantly attenuated seizures elicited by imipramine and significantly attenuated the seizure-enhancing effect of DOPs. alpha-Methyl-p-tyrosine and reserpine significantly attenuated seizures induced by imipramine. Disulfiram significantly protected mice against imipramine-induced seizures. However, DOPS significantly potentiated seizures induced by imipramine in disulfiram-pretreated animals. Clonidine effectively protected mice against imipramine-induced seizures. Idazoxan, on the other hand, significantly potentiated seizures induced by imipramine and significantly antagonised the protective effect of clonidine against the seizures. 5-HTP, PCPA, cyproheptadine, mianserin, ketanserin and trazodone did not affect imipramine-induced seizures to any significant extent. Physostigmine antagonised seizures induced by imipramine while atropine significantly potentiated the seizures, and significantly attenuated the protective effect of physostigmine against the seizures. These data suggest that enhancement and attenuation of central noradrenergic and cholinergic neurotransmissions respectively, and not 5-HT mechanisms, may underlie imipramine-induced seizures in mice.