Abstract
As part of our ongoing structure-activity studies of the vesicular acetylcholine transporter ligand 2-(4-phenylpiperidino)cyclohexanol (vesamicol, 1), 22 N-hydroxy(phenyl)alkyl derivatives of 3 beta-phenyltropane, 6, and 1-methylspiro[1H-indoline-3,4'-piperidine], 7, were synthesized and tested for binding in vitro. Although a few compounds displayed moderately high affinity for the vesicular acetylcholine transporter, no compound was more potent than the prototypical vesicular acetylcholine transporter ligand vesamicol. However, a few derivatives of 6 displayed higher affinity for the dopamine transporter than cocaine. We conclude that modification of the piperidyl fragment of 1 will not lead to more potent vesicular acetylcholine transporter ligands.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Anesthetics, Local / metabolism
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Anesthetics, Local / pharmacology
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Animals
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Carrier Proteins / metabolism*
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Cocaine / metabolism
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Cocaine / pharmacology
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Dopamine Plasma Membrane Transport Proteins
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Guinea Pigs
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Kinetics
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Male
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Membrane Glycoproteins*
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Membrane Transport Proteins*
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Molecular Conformation
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Nerve Tissue Proteins*
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Neuromuscular Depolarizing Agents / chemical synthesis*
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Neuromuscular Depolarizing Agents / metabolism
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Neuromuscular Depolarizing Agents / pharmacology*
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Neurotransmitter Agents / chemical synthesis
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Neurotransmitter Agents / metabolism
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Neurotransmitter Agents / pharmacology
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Piperidines / chemical synthesis*
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Piperidines / metabolism
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Piperidines / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Tropanes / chemical synthesis*
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Tropanes / metabolism
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Tropanes / pharmacology*
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Vesicular Acetylcholine Transport Proteins
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Vesicular Transport Proteins*
Substances
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Anesthetics, Local
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Carrier Proteins
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Dopamine Plasma Membrane Transport Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Neuromuscular Depolarizing Agents
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Neurotransmitter Agents
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Piperidines
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Slc18a3 protein, rat
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Tropanes
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Vesicular Acetylcholine Transport Proteins
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Vesicular Transport Proteins
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vesamicol
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Cocaine