Hui F W, Krikun E, Smith A A
Eur J Pharmacol. 1978 May 1;49(1):87-93. doi: 10.1016/0014-2999(78)90225-x.
Neonatal mice were injected once daily with d,l-methadone in a dosage of 2 mg/kg. The remaining half of the litter was injected with saline. After one week the incorporation of labeled uridine and labeled leucine was significantly (P less than 0.05) reduced in skeletal muscle. Longer treatment with methadone impaired RNA and protein synthesis in liver, heart, skeletal muscle and brain. The percentage reduction RNA was log-dose related. When methadone was discontinued for 1 week following 4 weeks of treatment, incorporation of precursors into RNA and protein was found to be normal. A specific opioid effect is suggested by the finding that naltrexone or in part, naloxone, given concomitantly with with the methadone prevents development of the biochemical lesion.
新生小鼠每天注射一次剂量为2毫克/千克的消旋美沙酮。同窝的另一半小鼠注射生理盐水。一周后,骨骼肌中标记尿苷和标记亮氨酸的掺入显著减少(P<0.05)。用美沙酮进行更长时间的治疗会损害肝脏、心脏、骨骼肌和大脑中的RNA和蛋白质合成。RNA减少的百分比与对数剂量相关。在治疗4周后停用美沙酮1周,发现前体掺入RNA和蛋白质的情况正常。同时给予纳曲酮或部分纳洛酮与美沙酮可预防生化损伤的发生,这一发现提示了一种特定的阿片样物质效应。