Sobel B F, Hutchinson A C, Diamond H F, Etkind S A, Ziervogel S D, Ferrari C M, Riley A L
Department of Psychology, American University, Washington, DC 20016, USA.
Neurotoxicol Teratol. 1998 Jul-Aug;20(4):459-63. doi: 10.1016/s0892-0362(97)00132-3.
Cocaethylene, the metabolite of cocaine produced only in the presence of alcohol, produces a number of pharmacological, physiological, and behavioral effects. It also has a range of toxicological consequences, the most severe being lethality. Given that the assessments of cocaethylene lethality have been limited to mice, the present study assessed the lethality of cocaethylene in rats. Further, because of within-species sex differences with its parent compound, cocaine, cocaethylene lethality was also examined in both females and males. Specifically, female and male rats were injected IP with 75, 87, 100, 115, and 133 mg/kg cocaethylene and observed over a 24-h period. Deaths were dose dependent and occurred within 30 min for both females and males. For females, the LD50 was 96 mg/kg; for males, the LD50 was 70 mg/kg. The percentage of rats displaying severe effects (i.e., seizure and death) increased with dose across all postinjection times. Further, these effects occurred earlier as dose increased. Differences in the LD50 for rats and mice, as well as the greater sensitivity to cocaethylene in male rats, are discussed.
可卡乙碱是仅在有酒精存在时由可卡因产生的代谢产物，会产生多种药理、生理和行为效应。它还会引发一系列毒理学后果，其中最严重的是致死性。鉴于对可卡乙碱致死性的评估仅限于小鼠，本研究评估了可卡乙碱对大鼠的致死性。此外，由于其母体化合物可卡因存在种内性别差异，本研究还考察了雌性和雄性大鼠对可卡乙碱的致死性。具体而言，对雌性和雄性大鼠腹腔注射75、87、100、115和133毫克/千克的可卡乙碱，并在24小时内进行观察。死亡呈剂量依赖性，雌性和雄性大鼠均在30分钟内死亡。对于雌性大鼠，半数致死量（LD50）为96毫克/千克；对于雄性大鼠，LD50为70毫克/千克。在注射后的所有时间点，出现严重效应（即癫痫发作和死亡）的大鼠百分比均随剂量增加而升高。此外，随着剂量增加，这些效应出现得更早。本文讨论了大鼠和小鼠LD50的差异，以及雄性大鼠对可卡乙碱更高的敏感性。
