N-HYDROXYALKYL DERIVATIVES OF 3-BETA-PHENYLTROPANE AND 1-METHYLSPIRO[1H-INDOLINE-3,4'-PIPERIDINE] - VESAMICOL ANALOGS WITH AFFINITY FOR MONOAMINE TRANSPORTERS

As part of our ongoing structure-activity studies of the vesicular ace tylcholine transporter ligand 2-(4-phenylpiperidino)cyclohexanol (vesa micol, 1), 22 N-hydroxy(phenyl)alkyl derivatives of 3 beta-phenyltropa ne, 6, and 1-methylspiro[1H-indoline-3,4'-piperidine], 7, were synthes ized and tested for binding in vitro. Although a few compounds display ed moderately high affinity for the vesicular acetylcholine transporte r, no compound was more potent than the prototypical vesicular acetylc holine transporter ligand vesamicol. However, a few derivatives of 6 d isplayed higher affinity for the dopamine transporter than cocaine. We conclude that modification of the piperidyl fragment of 1 will not le ad to more potent vesicular acetylcholine transporter ligands.