Naltrindole, a selective delta-opioid receptor antagonist, potentiates the lethal effects of cocaine by a central mechanism of action.
Naltrindole, a selective delta-opioid receptor antagonist, potentiates the lethal effects of cocaine by a central mechanism of action.
复制标题
纳曲吲哚是一种选择性 δ-阿片受体拮抗剂，通过中心作用机制增强可卡因的致命作用。
DOI：
10.1016/s0014-2999(97)01090-x
复制
发表时间：
1997
影响因子：
5
通讯作者：
Holtzman,SG
中科院分区：
文献类型：
--
作者：
Patterson,AB;Gordon,FJ;Holtzman,SG
在接受可卡因持续静脉输注直至死亡的未受限制的未麻醉大鼠中，探索了选择性δ阿片受体拮抗剂纳曲吲哚对可卡因毒性和致死作用的增强作用。脑池内注射纳曲吲哚（3.0-30 μg），而静脉注射（30-300 μ g），可卡因的致死量呈剂量依赖性降低。注射非选择性阿片类拮抗剂纳洛酮后，可卡因的致死剂量也有所下降，但纳洛酮没有下降。然而，在接受纳曲吲哚的大鼠中，无论给药途径、纳洛酮或纳曲酮如何，可卡因的产毒剂量均呈剂量依赖性降低。相比之下，可卡因对心率的影响仅通过中枢给药纳曲吲哚或静脉内纳曲酮改变，30 μg纳曲吲哚和10 mg/kg纳曲酮的剂量消除了可卡因的心动过缓作用。尽管如此，纳曲吲哚和纳曲酮都没有改变可卡因的高血压作用。较高剂量的纳曲吲哚（100 μg i.c.）产生显著的心率和平均动脉压增加，并且没有与可卡因结合进行测试。由于可卡因的致死剂量仅在脑池内给药时才降低，因此纳曲吲哚对可卡因致死作用的增强是通过一种可能涉及心血管功能变化的中枢作用机制。
The potentiation of the toxic and lethal effects of cocaine by the selective δ-opioid receptor antagonist naltrindole was explored in unrestrained, unanesthetized rats that received a continuous intravenous infusion of cocaine until death. The lethal dose of cocaine was lowered dose dependently in animals administered naltrindole intracisternally (3.0–30 μg), but not intravenously (30–300 μg). There was also a decrease in the lethal dose of cocaine following an injection of the nonselective opioid antagonist naltrexone, but not naloxone. However, the seizure-producing dose of cocaine was decreased dose dependently in rats that received naltrindole, regardless of the route of administration, naloxone, or naltrexone. In contrast, the effect of cocaine on heart rate was altered only by centrally administered naltrindole or intravenous naltrexone, with a dose of 30 μg naltrindole and 10 mg/kg naltrexone abolishing the bradycardic effect of cocaine. Despite this, neither naltrindole nor naltrexone changed the hypertensive effect of cocaine. Higher doses of naltrindole (100 μg i.c.) produced significant increases in heart rate and mean arterial pressure and were not tested in combination with cocaine. Because the lethal dose of cocaine was reduced only when naltrindole was administered intracisternally, the potentiation of the lethal effects of cocaine by naltrindole is through a central mechanism of action that may involve changes in cardiovascular function.