Abstract
N-Norcocaine (2) and six N-nor-3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters (4a-f) were synthesized by N-demethylation of cocaine (1) and the appropriate 3 beta-(substituted phenyl)-tropane analogues (3a-f) with alpha-chloroethyl chloroformate. Radioligand binding affinities of 2 and 4a-f at the DA, 5-HT, and NE transporter were measured and compared to those of 1 and 3a-f. N-Demethylation produced relatively small effects at the DA transporter. In contrast, 4-19-fold and 2-44-fold enhanced affinity at the serotonin and norepinephrine transporter resulted from demethylation. N-Nor-3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (4d) with an IC50 = 0.36 nM showed the greatest affinity for the serotonin transporter. However, N-nor-3 beta-(4'-ethylphenyl)tropane-2 beta-carboxylic acid methyl ester (4e) showed the greatest selectivity for the serotonin transporter.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Carrier Proteins / metabolism*
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Cocaine / analogs & derivatives*
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Cocaine / chemistry
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Cocaine / metabolism
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Dopamine Plasma Membrane Transport Proteins
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Male
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Membrane Glycoproteins / metabolism*
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Membrane Transport Proteins*
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Molecular Structure
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Nerve Tissue Proteins*
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Norepinephrine Plasma Membrane Transport Proteins
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Rats
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Rats, Sprague-Dawley
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Serotonin Plasma Membrane Transport Proteins
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Structure-Activity Relationship
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Symporters*
Substances
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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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N-nor-3-(4'-ethylphenyl)tropane-2-carboxylic acid methyl ester
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Nerve Tissue Proteins
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Norepinephrine Plasma Membrane Transport Proteins
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Serotonin Plasma Membrane Transport Proteins
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Slc6a2 protein, rat
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Slc6a4 protein, rat
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Symporters
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N-nor-3-(4'-iodophenyl)tropane-2-carboxylic acid methyl ester
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norcocaine
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Cocaine