Neuropharmacology and Neurotoxicology2′-Substitution of cocaine selectively enhances dopamine and norepinephrine transporter bindingSeale, Thomas W.1,2,4; Avor, Kwasi3; Singh, Satendra3; Hall, Nicolas1,3; Chan, Hui-Min1; Basmadjian, Garo P.3Author Information 1Department of Pediatrics, Room 2B-251 CHO, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA 2Department of Psychiatry and Behavioral Science, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA 3Department of Medicinal Chemistry and Pharmaceutics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA 4Corresponding Author and Address: Thomas W. Seale, Department of Pediatrics, Room 2B-251 CHO, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA Received 24 July 1997; accepted 28 August 1997 NeuroReport: November 10th, 1997 - Volume 8 - Issue 16 - p 3571-3575 Buy Abstract FEW studies have characterized the effect of substituents at the 2′-position of cocaine on transporter binding potency and selectivity. We synthesized 2′-OH-, 2′-Fand 2′-acetoxy-cocaines and compared their binding potencies for rat dopamine, norepinephrine and 5hydroxytryptamine transporters to cocaine, 3′-OH-, 4′-OH-, 2′-OH,4′-I-cocaine derivatives, and to the transporter selective ligands WIN 35,428, nisoxetine and paroxetine. Unlike most substitutions, 2′-OHand 2′-acetoxy-groups increased cocaine's binding potency for the dopamine transporter (10and 4-fold, respectively). These substituents also enhanced binding to the norepinephrine transporter (52and 35-fold, respectively) but had less effect on 5-hydroxytryptamine transporter binding. 2′-Hydroxylation also enhanced binding of 4′-I cocaine, an analog with low DA binding potency. The ability of 2′-substituents to substantially increase cocaine binding potency and to alter selectivity for brain transporters indicates the potential importance of the 2′-position in transporter binding. © Lippincott-Raven Publishers.