Studies of selected phenyltropanes at monoamine transporters

• Published in: Drug and alcohol dependence 1999-08, Vol.56 (1), p.9-15
• Main Authors: Kuhar, Michael J, McGirr, Kathleen M, Hunter, Richard G, Lambert, Philip D, Garrett, Bridgette E, Carroll, F.Ivy
• Format: Article
• Language: English
• Subjects: 3-Phenyltropane analogues; Adult; Aged; Animals; Binding, Competitive - drug effects; Biological and medical sciences; Carrier Proteins - drug effects; Carrier Proteins - physiology; Caudate Nucleus - drug effects; Cocaine; Cocaine - analogs & derivatives; Cocaine - pharmacology; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Humans; Macaca mulatta; Male; Medication; Membrane Glycoproteins - drug effects; Membrane Glycoproteins - physiology; Membrane Transport Proteins; Middle Aged; Monoamine transporters; Nerve Tissue Proteins; Norepinephrine Plasma Membrane Transport Proteins; Putamen - drug effects; Rats; Rats, Sprague-Dawley; Rhombencephalon - drug effects; Selected phenyltropanes; Serotonin Plasma Membrane Transport Proteins; Symporters; Tropanes - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/S0376-8716(99)00005-8

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.