| Behavioral and biochemical investigations of bupropion metabolites. | |
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MedLine Citation:
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PMID: 12909199 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mikhail L Bondarev; Tatiana S Bondareva; Richard Young; Richard A Glennon |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: European journal of pharmacology Volume: 474 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-08-11 Completed Date: 2004-05-11 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 85-93 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 554A Smith Building 410 N. 12th Street, Box 980540, Richmond, VA 23298-0540, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amphetamine
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administration & dosage Animals Antidepressive Agents, Second-Generation / metabolism, pharmacology* Behavior, Animal / drug effects* Binding, Competitive Bupropion / metabolism, pharmacology* Cell Line Discrimination Learning / drug effects* Humans Male Nicotine / administration & dosage Radioligand Assay Rats Rats, Sprague-Dawley Receptors, Nicotinic / genetics, metabolism* Rubidium Radioisotopes Transfection |
| Grant Support | |
ID/Acronym/Agency:
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DA 01642/DA/NIDA NIH HHS; DA 05274/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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