Derlet R W, Albertson T E, Rice P
Department of Internal Medicine, University of California, School of Medicine, Davis 95616.
Life Sci. 1990;47(9):821-7. doi: 10.1016/0024-3205(90)90555-6.
The effect of SCH 23390, a dopamine-one (D1) antagonist, in preventing acute toxicity induced by lethal doses of cocaine, d-amphetamine, and methamphetamine was studied in the rat. Animals were first pretreated with SCH 23390 (0.0, 0.5, 1.0, and 2.5 mg/kg, i.p.) and then were challenged with cocaine (70 mg/kg, i.p., an LD85), d-amphetamine (75 mg/kg, i.p., an LD95), and methamphetamine (100 mg/kg, i.p., an LD90). SCH 23390 did not alter the incidence of stimulant-induced seizures compared to the vehicle controls. Significant protection against cocaine-induced death was afforded only by the lowest dose of SCH 23390 tested. Significant protection against d-amphetamine-induced death was provided by all doses, with a dose dependent effect noted so that the incidence decreased from 95% for vehicle to 30% (p less than or equal to 0.01) with 2.5 mg/kg SCH 23390 pretreatment. No statistically significant reduction in the incidence of methamphetamine-induced death was seen with SCH 23390 pretreatment. The ability of SCH 23390 to protect against d-amphetamine, but apparently not against methamphetamine-induced death, suggests that different mechanisms of toxicity may exist between these drugs at high doses.
在大鼠中研究了多巴胺-1（D1）拮抗剂SCH 23390预防致死剂量可卡因、右旋苯丙胺和甲基苯丙胺所致急性毒性的作用。动物首先用SCH 23390（0.0、0.5、1.0和2.5mg/kg，腹腔注射）进行预处理，然后分别用可卡因（70mg/kg，腹腔注射，LD85）、右旋苯丙胺（75mg/kg，腹腔注射，LD95）和甲基苯丙胺（100mg/kg，腹腔注射，LD90）进行激发试验。与溶媒对照组相比，SCH 23390未改变兴奋剂诱发惊厥的发生率。仅在所测试的最低剂量的SCH 23390下，对可卡因诱导的死亡有显著保护作用。所有剂量的SCH 23390均对右旋苯丙胺诱导的死亡有显著保护作用，呈现剂量依赖性效应，即经2.5mg/kg SCH 23390预处理后，发生率从溶媒组的95%降至30%（p≤0.01）。经SCH 23390预处理后，甲基苯丙胺诱导的死亡发生率未见统计学显著降低。SCH 23390对右旋苯丙胺诱导的死亡有保护作用，但对甲基苯丙胺诱导的死亡无明显保护作用，这表明这些药物在高剂量时可能存在不同的毒性机制。
