Hsu W H, Smith B E, Hollingworth R M
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
Life Sci. 1988;43(23):1897-904. doi: 10.1016/s0024-3205(88)80007-9.
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.
在戊巴比妥麻醉的大鼠中，研究了静脉注射杀虫脒（CDM，0.3 - 10毫克/千克）及其代谢产物去甲基杀虫脒（DCDM，0.03 - 1毫克/千克）和双去甲基杀虫脒（DDCDM，0.1 - 3毫克/千克）时的瞳孔和心脏反应。CDM和DCDM均引起剂量依赖性瞳孔散大和心动过缓，且DCDM引起这些效应的效力比CDM高10倍。相比之下，DDCDM未引起瞳孔散大或心动过缓。α2 - 肾上腺素能受体拮抗剂咪唑克生（0.2毫克/千克，静脉注射）消除或降低了CDM和DCDM引起的瞳孔散大和心动过缓，而α1 - 肾上腺素能受体拮抗剂哌唑嗪（1.5毫克/千克，静脉注射）未改变CDM和DCDM的这些效应。在首次注射CDM前10分钟腹腔注射酶促去甲基化抑制剂SKF 525 - A（50毫克/千克），未能降低CDM的效应。结果表明：1）CDM和DCDM的散瞳和心动过缓效应由α2 - 肾上腺素能受体介导；2）CDM的单去甲基化增加了其α2 - 肾上腺素能受体激动活性，但CDM的双去甲基化消除了这些活性；3）CDM可在不经历去甲基化过程的情况下发挥α2 - 肾上腺素能受体激动活性。
