Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 492, Issue 1, Pages 21-26Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2004.03.037
Keywords
cocaine; convulsion; lethality; sigma receptor; toxicity
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Funding
- NIDA NIH HHS [DA11979, DA13978] Funding Source: Medline
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Previous studies have shown that BD1008 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) and related analogs attenuate the toxicity and stimulant effects of cocaine through antagonism of sigma receptors. In the present study, six analogs of BD1008 (UMB 98-103) were synthesized and evaluated in receptor binding and behavioral studies. Competition binding studies confirmed that all six compounds have high affinity for sigma(1) receptors, moderate affinity for sigma(2) receptors, and low to negligible affinity for monoamine transporters, opioid, N-methyl-D-aspartate, dopamine, and 5-HT receptors. In behavioral pharmacological studies, pretreatment of mice with UMB 100, UMB 101, or UMB 103 significantly attenuated cocaine-induced convulsions and lethality. Together with earlier studies, the data suggest that analogs of BD1008 are promising medication development leads for reducing the toxicity of cocaine. (C) 2004 Elsevier B.V. All rights reserved.
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