Madras B K, Kamien J B, Fahey M A, Canfield D R, Milius R A, Saha J K, Neumeyer J L, Spealman R D
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.
Pharmacol Biochem Behav. 1990 Apr;35(4):949-53. doi: 10.1016/0091-3057(90)90384-t.
The binding properties of three N-modified fluorophenyltropane analogs of cocaine were compared in competition experiments with [3H]cocaine. All three analogs displaced specifically bound [3H]cocaine from caudate-putamen membranes of cynomolgus monkeys with affinities exceeding that of cocaine. The compound with the highest affinity, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)-N-allyl-nortropane, (N-allyl-CFNT) was about three times more potent than cocaine. N-Allyl-CFNT also had cocaine-like interoceptive effects and was about three times more potent than cocaine in squirrel monkeys trained to discriminate cocaine from vehicle in an operant drug discrimination procedure. The results suggest that N-modified fluorophenyltropane derivatives may be useful precursors for development of pharmacological probes for cocaine receptors.
在与[3H]可卡因的竞争实验中，比较了三种可卡因的N-修饰氟苯基托烷类似物的结合特性。所有三种类似物都以超过可卡因的亲和力，从食蟹猴的尾状核-壳核膜上特异性取代结合的[3H]可卡因。亲和力最高的化合物，2β-甲氧基羰基-3β-(4-氟苯基)-N-烯丙基去甲托烷，(N-烯丙基-CFNT)的效力约为可卡因的三倍。N-烯丙基-CFNT也具有类似可卡因的内感受作用，在操作性药物辨别程序中训练以区分可卡因和赋形剂的松鼠猴中，其效力约为可卡因的三倍。结果表明，N-修饰的氟苯基托烷衍生物可能是开发可卡因受体药理学探针的有用前体。
