PERINATAL COCAINE INTOXICATION AND TREATMENT

这项研究项目的主要目标是提供一个 对可卡因中与怀孕和性别有关的差异的理解 醉酒，这是科学上很少关注的问题，并 检测钙通道阻滞剂的解毒和解冻效果 硝苯地平治疗可卡因中毒和早产。自.以来 可卡因被血浆胆碱酯酶水解，因为卵巢 类固醇似乎可以调节胆碱酯酶的合成，剂量为 在胎儿中产生中毒的可卡因应该是不同的， 怀孕和未怀孕的雌性以及成年雄性。长期地 将使用仪器化的大鼠和豚鼠模型，动脉和 静脉导管、心电电极以及某些动物的宫内导管 为持续监测生理参数而植入的导管 以及对药物的管理。将获得血浆和组织样本 用于确定可卡因浓度，这将与 生理参数和行为变化。比较门槛 男性和男性的急性可卡因毒性和血浆胆碱酯酶活性 怀孕和经激素操纵的非怀孕女性将接受检查 阐明激素机制在可卡因中毒中的作用。硝苯地平 将评估可卡因过量的解毒效果，以及其 宫缩作用对可卡因引起的妊娠子宫收缩的影响 老鼠，这可能有助于防止早产。最后，有益的 可卡因宫内清除对胎儿的影响-- 过量服药的母亲将被评估。 从这些研究中获得的数据不仅将有助于 了解怀孕期间滥用可卡因的风险，但会 也导致了预防可卡因引起的早产和 新生儿可卡因中毒。

The principal objectives of this research project are to provide an understanding of pregnancy- and gender-related differences in cocaine intoxication, to which little scientific attention has been paid, and to test the antidotal and tocolytic efficacy of the calcium channel blocker nifedipine on cocaine-induced intoxication and premature labor. Since cocaine is hydrolyzed by plasma cholinesterase, and because ovarian steroids appear to modulate the synthesis of cholinesterases, dosages of cocaine that produce intoxication should be different in the fetus, pregnant and nonpregnant female, as well as in the adult male. Chronically instrumented rat and guinea pig models will be used, with arterial and venous catheters, ECG electrodes and in some animals, intrauterine catheters implanted for continuous monitoring of physiological parameters and administration of drugs. Plasma and tissue samples will be obtained for determination of cocaine concentrations, which will be correlated with physiological parameters and behavioral changes. The comparative threshold of acute cocaine toxicity and plasma cholinesterase activity in males and pregnant and hormonally manipulated nonpregnant females will be examined to clarify the role of hormonal mechanisms in cocaine toxicity. Nifedipine's antidotal efficacy in cocaine overdose will be assessed, as will its tocolytic effect on cocaine-induced uterine contractions in the pregnant rat, which may serve to prevent premature labor. Finally, the beneficial effect of intrauterine clearance of cocaine upon the fetus of the cocaine- overdosed mother will be evaluated. The data obtained from these studies will not only contribute to a greater understanding of the risks of the cocaine abuse during pregnancy, but will also lead to methods of preventing both cocaine-induced premature labor and neonatal cocaine intoxication.