The goal of this project is to test the feasibility of using a group of phenyltropane analogs of cocaine as medications for cocaine addicts. The goal of these past two years has been to see if these compounds interact with cocaine receptors in the expected way and to test whether or not cocaine receptors from rats, monkeys and humans were similar. Our findings indicate that the selected compounds were indeed suitable in that they had high and selective affinity for cocaine receptors. Moreover, we showed for this group of compounds, that cocaine receptors in rat, monkey and human brain tissue obtained at autopsy, were similar. FUNDING ONDCP / OND6069 $178,713 09/26/96 - 09/26/01 PUBLICATIONS Carroll, F.I., Lewin, A.H. and Kuhar, M.J. 3(-Phenyl-2(-substituted tropanes - An SAR analysis. Med. Chem. Res. 8(1/2):59-65, 1998. Dworkin, S.I., Lambert, P., Sizemore, G.M., Carroll, F.I. and Kuhar, M.J. RTI-113 administration reduces cocaine self-administration at high occupancy of dopamine transporter. Synapse 30:49-55, 1998. Houlihan, W.J., Boja, J.W., Kopajtic, T.A., Kuhar, M.J., Degrado, S.J. and Toledo, L. Positional isomers and analogs of mazindol as potential inhibitors of the cocaine binding site on the dopamine transporter site. Med. Chem. Res. 8(1/2):77-90, 1998. Keverline-Frantz, K.I., Boja, J.W., Kuhar, M.J., Abraham, P., Burgess, J.P., Lewin, A.H. and Carroll, F.I. Synthesis and ligand binding of tropane ring analogues of paroxetine. J. Med. Chem. 41:247-258, 1998. Kuhar, M.J. Recent biochemical studies of the dopamine transporter - A CNS drug target. Life Sci. 62(17/18):1573-1575, 1998. Persico, A.M., Reich, S., Henningfield, J.E., Kuhar, M.J. and Uhl, G.R. Parkinsonian patients report blunted subjective effects of methylphenidate. Exp. Clin. Psychopharmacol. 6:54-63, 1998. P51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center
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