Langley A E, Smith S G, Zeid R L
Proc Soc Exp Biol Med. 1984 Sep;176(4):350-5. doi: 10.3181/00379727-176-41882.
In isolated rat hearts L-alphacetylmethadol (LAAM) produced a concentration-dependent decrease in the spontaneous beating rate. This effect was completely prevented by 1.0 microM atropine. Chronic treatment of rats with LAAM increased the number of striatal dopamine receptors measured by [3H]spiroperidol binding. The affinity of these binding sites for [3H]spiroperidol was unchanged by LAAM treatment. There were no significant changes in the number or affinity of binding sites for the labeled muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB) with chronic LAAM treatment. The ability of LAAM, nor-LAAM, or dinor-LAAM to antagonize the binding of [3H]spiroperidol (40 pM) or [3H]QNB (125 pM) to striatal membrane fragments was tested. The measured affinity constants for LAAM and metabolites were 100-3000 times higher than the affinity constants of unlabeled spiroperidol at [3H]spiroperidol binding sites. The affinity constants of LAAM and metabolites at muscarinic binding sites were 10-20 times higher than pilocarpine and 5000-8000 times higher than atropine. These results suggest that LAAM can produce some of its effects by acting as a weak agonist at muscarinic receptor sites.
在离体大鼠心脏中，左旋α-乙酰美沙多（LAAM）使自发搏动率呈浓度依赖性降低。1.0微摩尔阿托品可完全阻断这一效应。用LAAM长期治疗大鼠可增加通过[3H]螺哌啶醇结合测定的纹状体多巴胺受体数量。LAAM处理后，这些结合位点对[3H]螺哌啶醇的亲和力未发生改变。长期用LAAM治疗后，标记的毒蕈碱拮抗剂[3H]喹核醇基苯甲酸酯（[3H]QNB）结合位点的数量和亲和力无显著变化。测试了LAAM、去甲LAAM或双去甲LAAM拮抗[3H]螺哌啶醇（40皮摩尔）或[3H]QNB（125皮摩尔）与纹状体膜片段结合的能力。所测得的LAAM及其代谢产物的亲和常数比未标记的螺哌啶醇在[3H]螺哌啶醇结合位点的亲和常数高100 - 3000倍。LAAM及其代谢产物在毒蕈碱结合位点的亲和常数比毛果芸香碱高10 - 20倍，比阿托品高5000 - 8000倍。这些结果表明，LAAM可通过作为毒蕈碱受体位点的弱激动剂发挥其部分作用。
