Holtzman S G
Pharmacol Biochem Behav. 1979 Apr;10(4):565-8. doi: 10.1016/0091-3057(79)90234-x.
The discriminative stimulus properties of l-alpha-acetylmethadol (LAAM), its metabolities 1-alpha-acetyl-N-normethadol (NorLaam) and l-alpha-acetyl-N,N-dinormethadol (DiNorLAAM), and methadone were evaluated in rats trained to discriminate between saline and morphine in a two-choice discrete-trial avoidance paradigm. All four compounds produced dose-related increases in the number of trials completed on the morphine-appropriate choice lever after either SC or oral administration indicating that the discriminative stimulus properties of the four compounds and morphine are qualitatively similar. LAAM and DiNorLAAM had a slow onset and long duration of action, and an oral: parenteral potency ratio of 1:3. NorLaam had a more rapid onset and shorter duration of action and was more potent following SC administration than either LAAM or DiNorLAAM; its oral: parenteral potency ratio was 1:10. These results are consistent with evidence from other studies that the pharmacologic activity of LAAM is dependent upon the conversion of LAAM to an active metabolite, probably NorLAAM. The similarities between DiNorLAAM and LAAM suggest that the discriminative stimulus effects of the former compound are also attributable to a metabolite.
在一个两选择离散试验回避范式中，对训练来区分生理盐水和吗啡的大鼠评估了左旋α-乙酰美沙多（LAAM）、其代谢产物1-α-乙酰基-N-去甲美沙多（NorLAAM）和1-α-乙酰基-N,N-二去甲美沙多（DiNorLAAM）以及美沙酮的辨别刺激特性。在皮下或口服给药后，所有这四种化合物都使在吗啡适宜选择杆上完成的试验次数出现剂量相关的增加，表明这四种化合物和美沙酮的辨别刺激特性在性质上相似。LAAM和DiNorLAAM起效缓慢且作用持续时间长，口服与肠胃外给药效力比为1:3。NorLAAM起效更快且作用持续时间更短，皮下给药后比LAAM或DiNorLAAM更有效；其口服与肠胃外给药效力比为1:10。这些结果与其他研究的证据一致，即LAAM的药理活性依赖于LAAM转化为活性代谢产物，可能是NorLAAM。DiNorLAAM和LAAM之间的相似性表明，前一种化合物的辨别刺激效应也归因于一种代谢产物。
