Hampl R, Bicíková M, Motlík K, Stárka L
Research Institute of Endocrinology, Praha, Czechoslovakia.
Endocrinol Exp. 1987 Sep;21(3):229-35.
Etomidate, an imidazole derived hypnotic was applied to rats in order to find out whether repeated treatment with the drug, in doses exceeding those usually given to human, does alter adrenal morphology and function in terms of corticosterone and 11 beta-hydroxyandrostenedione (an androgen of exclusively adrenal origin) production, both in vivo and in vitro. A slight, dose-related decrease of plasma corticosterone and 11 beta-hydroxyandrostenedione was observed from etomidate concentrations 0.3 resp. 1.4 mg kg-1 body weight, respectively. In vitro, corticosterone production was reduced in the groups receiving 0.7 mg of the drug or more. Morphologically, only minute lipid hyperplasia was found after the highest dose of etomidate, associated with a significant increase of relative body weight. Administration of low dose of etomidate (approx. one half of that given usually to human) led to an increase of corticosterone production, indicating the reversibility of such effect. Etomidate did not stimulate enzymic oxidation of 11 beta-hydroxysteroids to the corresponding 11-oxosteroids, as do some blockers of 11 beta-hydroxylase.
依托咪酯是一种咪唑类衍生的催眠药，将其应用于大鼠，目的是查明用超过通常给予人类剂量的该药物进行反复治疗，是否会在体内和体外改变肾上腺形态以及皮质酮和11β - 羟基雄烯二酮（一种完全源自肾上腺的雄激素）产生方面的功能。分别从依托咪酯浓度0.3和1.4毫克/千克体重开始，观察到血浆皮质酮和11β - 羟基雄烯二酮有轻微的、与剂量相关的下降。在体外，接受0.7毫克或更多该药物的组中皮质酮产生减少。形态学上，在给予最高剂量依托咪酯后仅发现微小的脂质增生，同时相对体重显著增加。给予低剂量依托咪酯（约为通常给予人类剂量的一半）导致皮质酮产生增加，表明这种效应具有可逆性。依托咪酯不像某些11β - 羟化酶抑制剂那样刺激11β - 羟基类固醇酶氧化为相应的11 - 氧代类固醇。
