Misra A L, Mule S J
Am J Drug Alcohol Abuse. 1977;4(3):431-40. doi: 10.3109/00952997709002776.
Recurrent episodes of mild to severe opiate-like toxic effects were observed in 3 of 18 monkeys maintained on 2 mg/kg p.o. dose of LAAM on alternate days 3 times a week for up to one year. Despite antagonist administration and artificial respiration, the final toxic reaction in 3 LAAM sensitive monkeys progressed rapidly to cardio-respiratory arrest and death 3, 6, and 12 months after LAAM treatment. The blood chemistry and hematology were not significantly altered during chronic LAAM administration. Necropsy did not reveal any aberrant gross, histological or neuropathological features other than pulmonary edema. Differential rates of formation and elimination of active metabolites of LAAM may play a significant role in this potentially lethal toxicity. These findings may have important clinical implications for LAAM maintenance treatment programs.
在18只猴子中，有3只猴子每周三次、隔天口服2毫克/千克剂量的左旋-α-乙酰美沙酮，持续长达一年，期间观察到反复出现轻度至重度类阿片样毒性作用。尽管给予了拮抗剂并进行了人工呼吸，但3只对左旋-α-乙酰美沙酮敏感的猴子在接受左旋-α-乙酰美沙酮治疗后3、6和12个月，最终的毒性反应迅速发展为心肺骤停和死亡。在长期给予左旋-α-乙酰美沙酮期间，血液化学和血液学指标没有明显改变。尸检未发现除肺水肿外的任何异常大体、组织学或神经病理学特征。左旋-α-乙酰美沙酮活性代谢物形成和消除的差异速率可能在这种潜在的致命毒性中起重要作用。这些发现可能对左旋-α-乙酰美沙酮维持治疗方案具有重要的临床意义。
