The bradycardic and mydriatic effects of chlordimeform and its demethylated analogs in the rat: antagonism by idazoxan but not by prazosin.
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| Abstract |
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.
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| Authors | W H Hsu, B E Smith, R M Hollingworth |
| Journal | Life sciences (Life Sci) Vol. 43 Issue 23 Pg. 1897-904 ( 1988) ISSN: 0024-3205 [Print] Netherlands |
| PMID | 2849009 (Publication Type: Comparative Study, Journal Article) |
| Chemical References |
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