Moore K A, Lichtman A H, Poklis A, Borzelleca J F
Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0597, USA.
Drug Alcohol Depend. 1995 Aug;39(2):83-9. doi: 10.1016/0376-8716(95)01140-t.
Methamphetamine is a popular drug of abuse, readily synthesized in clandestine laboratories. Illicitly obtained methamphetamine is frequently impure, containing various purposefully added diluents and adulterants, as well as impurities of manufacture and origin. Few impurities have been studied in vivo and limited information exists concerning their pharmacology/toxicology. One such impurity of manufacture is alpha-benzyl-N-methylphenethylamine (BNMPA). Acute toxicity and spontaneous activity (locomotor) studies were conducted with this compound alone and in combination with S(+)-methamphetamine (METH) in male, ICR mice. In the acute toxicity studies, BNMPA was evaluated for convulsant activity. While BNMPA also produced some behavioral disturbances similar to those seen with methamphetamine (e.g., stereotopy) at doses greater than 30 mg/kg, no tonic-clonic convulsions were noted until pre-terminal convulsion at 50 mg/kg. METH alone produced tonic-clonic convulsions at terminal doses of 70 mg/kg. When BNMPA was given in combination with METH, there was no readily apparent change in the convulsion profile from that of METH given alone. In spontaneous activity studies, doses of BNMPA ranging from 1 mg/kg to 50mg/kg failed to alter locomotor activity significantly from controls though 5 mg/kg METH alone significantly increased spontaneous activity. In addition, increases in spontaneous activity elicited by 5 mg/kg METH were not affected when METH was given with 5 mg/kg BNMPA. While BNMPA appears to have toxic effects in the central nervous system (CNS), the failure to affect locomotor activity or alter either METH-induced increases in spontaneous activity or METH-induced convulsions suggests that the two agents are producing their effects through distinct mechanisms.
甲基苯丙胺是一种常见的滥用药物,很容易在秘密实验室中合成。非法获取的甲基苯丙胺通常不纯,含有各种故意添加的稀释剂和掺杂物,以及生产和来源的杂质。很少有杂质在体内进行过研究,关于它们的药理学/毒理学的信息有限。一种这样的生产杂质是α-苄基-N-甲基苯乙胺(BNMPA)。单独使用该化合物以及与S(+)-甲基苯丙胺(METH)联合,对雄性ICR小鼠进行了急性毒性和自发活动(运动)研究。在急性毒性研究中,评估了BNMPA的惊厥活性。虽然BNMPA在剂量大于30mg/kg时也产生了一些与甲基苯丙胺所见相似的行为紊乱(例如,刻板行为),但直到50mg/kg出现濒死前惊厥才观察到强直阵挛性惊厥。单独使用METH在终末剂量70mg/kg时产生强直阵挛性惊厥。当BNMPA与METH联合给药时,惊厥特征与单独给予METH相比没有明显变化。在自发活动研究中,剂量范围从1mg/kg至50mg/kg的BNMPA与对照组相比未能显著改变运动活性,尽管单独使用5mg/kg的METH显著增加了自发活动。此外,当5mg/kg的METH与5mg/kg的BNMPA一起给药时,5mg/kg的METH引起的自发活动增加不受影响。虽然BNMPA似乎对中枢神经系统(CNS)有毒性作用,但未能影响运动活性或改变METH诱导的自发活动增加或METH诱导的惊厥表明这两种药物通过不同的机制产生作用。