The bradycardic and mydriatic effects of chlordimeform and its demethylated analogs in the rat: antagonism by idazoxan but not by prazosin.

Pupillary and cardiac responses to i.v. injections of chlordimeform (CDM, 0.3-10 mg/kg), a formamidine insecticide, and its metabolites demethylchlordimeform (DCDM, 0.03-1 mg/kg) and didemethylchlordimeform (DDCDM, 0.1-3 mg/kg) were studied in rats anesthetized with pentobarbital. Both CDM and DCDM induced a dose-dependent mydriasis and bradycardia and DCDM was 10 times more potent than CDM in causing these effects. In contrast, DDCDM did not induce a mydriasis or bradycardia. The alpha 2-adrenoreceptor antagonist, idazoxan (0.2 mg/kg, i.v.) abolished or reduced CDM- and DCDM-induced mydriasis and bradycardia, whereas the alpha 1-adrenoreceptor antagonist, prazosin (1.5 mg/kg, i.v.) did not change these effects of CDM and DCDM. SKF 525-A (50 mg/kg, i.p.), an inhibitor of enzymatic demethylation, administered 10 min before the first dose of CDM, failed to reduce the effects of CDM. The results suggested: 1) the mydriatic and bradycardic effects of CDM and DCDM are mediated by alpha 2-adrenoreceptors, 2) the monodemethylation of CDM increases its alpha 2-adrenoreceptor agonistic activities, but the didemethylation of CDM abolishes these activities, and 3) CDM can exert alpha 2-adrenoreceptor agonistic activities without undergoing a demethylation process.