Studies of selected phenyltropanes at monoamine transporters.

Abstract

3-Phenyltropane analogues of cocaine are useful neurobiologic tools for examining mechanisms of neurotransmitter transporters and psychostimulant drugs. They are also potential substitute medications for psychostimulant abuse. In this study, 18 3-phenyltropane analogues were characterized in uptake and binding studies at dopamine (DAT), norepinephrine (NET) and serotonin (SERT) transporters from the rat, and in binding at DAT in rat, rhesus monkey, and human brain tissue. In rat brain tissue, potency in inhibiting uptake generally correlated with the potency in inhibiting binding at all three transporters suggesting that none of these compounds have antagonist properties. At the DAT, there was a significant correlation of inhibitory potencies between the rat and monkey, the monkey and human, and the rat and human transporters although some compounds showed some species difference. These findings suggest that with regard to the 3-phenyltropane series, there is generally little pharmacologic difference between DATs from the three species examined, although binding data from rat may not be a perfect predictor of uptake inhibition in human.