3-aryl-2-carbomethoxybicyclo[3,2,1]oct-2-enes inhibit WIN 35,428 binding potently and selectively at the dopamine transporter

The search for medications for cocaine abuse has focused upon the design of potential cocaine antagonists or cocaine substitutes which interact at the dopamine transporter of mammalian systems. This manuscript describes the s ynthesis and biological evaluation of 8-substituted 2-carbomethoxy-3-arylbi cyclo[3.2.1]oct-2-enes. These compounds prove potent and selective inhibito rs of the dopamine transporter. Their selectivity results primarily from a reduced inhibitory potency toward the serotonin transporter. This work supp orts the notion that the orientation of the 3-aryl ring in the bicyclo[3.2, 1]octane system affects the interaction of these molecules with the seroton in transporter far more markedly than it affects the interaction with the d opamine transporter. (C) 2000 Elsevier Science Ltd. All rights reserved.