Document Detail

Behavioral and biochemical investigations of bupropion metabolites.
MedLine Citation:
PMID:  12909199     Owner:  NLM     Status:  MEDLINE    
The stimulus effects of bupropion metabolites were examined in a drug discrimination procedure using (-)nicotine- and (+)amphetamine-trained rats. (+)- and (-)threohydrobupropion partially substituted in each group. R,R-hydroxybupropion produced vehicle-appropriate responding in (-)nicotine animals but, when given in combination with the training dose of (-)nicotine, resulted in an attenuated effect. S,S-Hydroxybupropion partially (66%) substituted for (-)nicotine. In (+)amphetamine-trained animals, S,S-hydroxybupropion (ED50=4.4 mg/kg) generalized completely and was similar in potency to bupropion (ED50=5.4 mg/kg). Bupropion and its metabolites lacked affinity for nicotinic acetylcholinergic receptors, but all antagonized (-)nicotine-induced 86Rb+ efflux in cells expressing alpha3beta4 nicotinic cholinergic receptors. S,S-Hydroxybupropion possessed affinity at the dopamine transporter comparable to bupropion, and was also found to bind at the norepinephrine transporter. Although it is unlikely that any metabolite isomer is chiefly responsible for the stimulus actions of bupropion, some probably play a role in the complex actions of this agent.
Mikhail L Bondarev; Tatiana S Bondareva; Richard Young; Richard A Glennon
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  European journal of pharmacology     Volume:  474     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-11     Completed Date:  2004-05-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  85-93     Citation Subset:  IM    
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 554A Smith Building 410 N. 12th Street, Box 980540, Richmond, VA 23298-0540, USA.
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MeSH Terms
Amphetamine / administration & dosage
Antidepressive Agents, Second-Generation / metabolism,  pharmacology*
Behavior, Animal / drug effects*
Binding, Competitive
Bupropion / metabolism,  pharmacology*
Cell Line
Discrimination Learning / drug effects*
Nicotine / administration & dosage
Radioligand Assay
Rats, Sprague-Dawley
Receptors, Nicotinic / genetics,  metabolism*
Rubidium Radioisotopes
Grant Support
Reg. No./Substance:
0/Antidepressive Agents, Second-Generation; 0/Receptors, Nicotinic; 0/Rubidium Radioisotopes; 300-62-9/Amphetamine; 34841-39-9/Bupropion; 54-11-5/Nicotine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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