PERINATAL COCAINE INTOXICATION AND TREATMENT

围产期可卡因中毒和治疗

• 批准号: 3213318
• 负责人: HISAYO O MORISHIMA
• 金额: $ 19.98万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3213318
• 关键词: acetylcholinesterase; anesthetics; beta antiadrenergic agent; calcium channel; cocaine; disease /disorder proneness /risk; drug abuse chemotherapy; drug adverse effect; embryo /fetus drug adverse effect; guinea pigs; hormone regulation /control mechanism; inhibitor /antagonist; laboratory rat; nifedipine; overdose; perinatal; plasma; pregnancy; steroid hormone

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.

本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了解 中毒，其中很少有科学的注意，并 测试钙通道阻滞剂的解毒和安胎效果 硝苯地平治疗可卡因中毒和早产。 以来 可卡因被血浆胆碱酯酶水解，并且由于卵巢 类固醇似乎调节胆碱酯酶的合成， 产生中毒的可卡因在胎儿中应该是不同的， 怀孕和未怀孕的女性，以及成年男性。 长期 将使用装有仪器的大鼠和豚鼠模型，动脉和 静脉导管、ECG电极和在某些动物中的宫内电极 植入导管用于连续监测生理参数 和药物管理。 将采集血浆和组织样本 用于确定可卡因浓度，这将与 生理参数和行为变化。 比较阈值 急性可卡因毒性和血浆胆碱酯酶活性的影响， 将检查妊娠和经尿道操作的非妊娠雌性动物， 阐明激素机制在可卡因毒性中的作用。 硝苯地平 将评估可卡因过量的解毒功效， 可卡因对孕妇宫缩的抑制作用 老鼠，这可能有助于防止早产。 最后，有益的 宫内清除可卡因对胎儿的影响- 将对过量用药的母亲进行评估。 从这些研究中获得的数据不仅有助于更大的 了解怀孕期间滥用可卡因的风险，但将 也导致预防可卡因引起的早产和 新生儿可卡因中毒