Paulus M P, Geyer M A
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093-0804.
Neuropsychopharmacology. 1992 Aug;7(1):15-31.
The effects of acute subcutaneous injections of methylenedioxy-substituted phenylalkylamines in rats were tested in an unconditioned motor behavior paradigm using the Behavioral Pattern Monitor (BPM). Based on a previously developed scaling hypothesis and the associated temporal and spatial scaling exponents (alpha and d), the effects of racemic and S(+) 3,4-methylenedioxyamphetamine (MDA), racemic, S(+) and R(-) 3,4-methylenedioxymethamphetamine (MDMA), racemic N-methyl-1-(1,3-benzodioxol-5yl)-2-butanamine (MBDB), racemic N-ethyl-3,4-methylenedioxyamphetamine (MDEA), 2,5-dimethoxy-4-iodoamphetamine, and methamphetamine were characterized using the d-alpha plane. Three distinct dose-response patterns were observed. 1) S(+) and (+/-)MDA had pronounced dose-dependent effects on the structure of motor behavior, which were characterized by long-straight path movements and minimal changes in the amount of motor behavior. 2) (+/-)MDMA and (+/-)MBDB dose-dependently changed patterns of movements towards long-straight paths together with dose-dependent increases in the amount of motor activity. 3) S(+)MDMA and (+/-)MDEA produced dose-related increases in the amount of motor activity with minimal changes of the movement patterns in the BPM. Comparisons with the existing drug discrimination, operant, and biochemical literature on these compounds lead to the conclusion that the observed effects in the d-alpha plane do not simply reflect the different effects of these compounds as dopamine or serotonin (5-HT) releasers or reuptake inhibitors and do not parallel their different abilities to exhibit hallucinogen-like effects. Instead, indirect 5-HT1 effects appear to contribute substantially to the differential changes in the amount and structure of motor behavior induced by the phenylalkylamines. This conclusion may provide an encouraging rationale to develop postsynaptically effective "entactogens," a potential new drug category as adjunctive psychotherapeutics.
在使用行为模式监测仪（BPM）的非条件运动行为范式中，测试了大鼠急性皮下注射亚甲二氧基取代的苯烷基胺的效果。基于先前提出的标度假设以及相关的时间和空间标度指数（α和d），使用d-α平面表征了外消旋和S(+) 3,4-亚甲二氧基苯丙胺（MDA）、外消旋、S(+)和R(-) 3,4-亚甲二氧基甲基苯丙胺（MDMA）、外消旋N-甲基-1-(1,3-苯并二氧杂环戊烯-5-基)-2-丁胺（MBDB）、外消旋N-乙基-3,4-亚甲二氧基苯丙胺（MDEA）、2,5-二甲氧基-4-碘苯丙胺和甲基苯丙胺的效果。观察到三种不同的剂量反应模式。1）S(+)和(+/-)MDA对运动行为结构有明显的剂量依赖性影响，其特征是直线运动路径长，运动行为量变化最小。2）(+/-)MDMA和(+/-)MBDB剂量依赖性地改变了向直线路径的运动模式，同时运动活动量呈剂量依赖性增加。3）S(+)MDMA和(+/-)MDEA使运动活动量呈剂量相关增加，而BPM中的运动模式变化最小。与关于这些化合物的现有药物辨别、操作性和生化文献进行比较后得出结论，在d-α平面中观察到的效果并非简单地反映这些化合物作为多巴胺或5-羟色胺（5-HT）释放剂或再摄取抑制剂的不同效果，也与它们表现出致幻样效果的不同能力不平行。相反，间接的5-HT1效应似乎在很大程度上导致了苯烷基胺引起的运动行为量和结构的差异变化。这一结论可能为开发突触后有效“触觉致幻剂”提供令人鼓舞的理论依据，“触觉致幻剂”作为辅助心理治疗药物是一种潜在的新药物类别。
