Bupropion is a nicotinic antagonist
Abstract
Neuronal nicotinic receptors are ligand-gated ion channels of the central and peripheral central nervous system that regulate synaptic activity from both pre- and postsynaptic sites. The present study establishes the acute interaction of bupropion, an antidepressant agent that is also effective in nicotine dependence, with nicotine and nicotinic receptors using different in vivo and in vitro tests. Bupropion was found to block nicotine's antinociception (in two tests), motor effects, hypothermia, and convulsive effects with different potencies in the present investigation, suggesting that bupropion possesses some selectivity for neuronal nicotinic receptors underlying these various nicotinic effects. In addition, bupropion blocks nicotine activation of alpha(3)beta(2), alpha(4)beta(2), and alpha(7) neuronal acetylcholine nicotinic receptors (nAChRs) with some degree of selectivity. It was approximately 50 and 12 times more effective in blocking alpha(3)beta(2) and alpha(4)beta(2) than alpha(7.) This functional blockade was noncompetitive, because it was insurmountable by increasing concentration of ACh in the nAChRs subtypes tested. Furthermore, bupropion at high concentration failed to displace brain [(3)H]nicotine binding sites, a site largely composed of alpha(4)beta(2) subunit combination. Given the observation that bupropion inhibition of alpha(3)beta(2) and alpha(4)beta(2) receptors exhibits voltage-independence properties, bupropion may not be acting as an open channel blocker. These effects may explain in part bupropion's efficacy in nicotine dependence. Our present findings suggest that functional blockade of neuronal nAChRs are useful in nicotine dependence treatment.
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Bupropion inhibits the function of α3β2-, α4β2-, and α7-nAChRs expressed in Xenopus oocytes.
“Bupropion inhibits the function of α3β2-, α4β2-, and α7-nAChRs heterologously expressed in Xenopus oocytes [219].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [219]
Bupropion non-competitively inhibits carbamylcholine-induced 86Rb+ efflux from human neuroblastoma cells expressing α3β4-containing nAChRs.
“It also non-competitively inhibits carbamylcholine-induced 86Rb+ efflux from human neuroblastoma cells expressing α3β4-containing nAChRs [218].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [218]
Bupropion is a non-competitive antagonist at many nAChR subtypes.
“Bupropion also functions as a non-competitive antagonist at many nAChR subtypes [218].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [218]
Bupropion is a noradrenergic reuptake inhibitor and also a noncompetitive nAChR antagonist.
“bupropion is a noradrenergic reuptake inhibitor but also a noncompetitive nAChR antagonist (Slemmer et al., 2000).”
From The duration of nicotine withdrawal-associated deficits in contextual fear conditioning parallels changes in hippocampal high affinity nicotinic acetylcholine receptor upregulation (2012) · cites this paper as Slemmer et al., 2000
Commonly used antidepressants can act as α4β2* nAChR antagonists in cell-based assays.
“commonly used antidepressants can also act as α4β2* nAChR antagonists in cell-based assays (Shytle et al., 2002; Slemmer et al., 2000)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Slemmer et al., 2000
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- Authors
- Slemmer, J. E., Martin, B. R., & Damaj, M. I.
- Affiliations
- Virginia Commonwealth University (US)
- ORCID
- Damaj, M. Imad
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 295
- Issue
- 1
- Pages
- 321-327
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2157144772
- Cited by
- 509
- References
- 26
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 6 · 2023: 15 · 2022: 10 · 2021: 11 · 2020: 18 · 2019: 11 · 2018: 22 · 2017: 11 · 2016: 18 · 2015: 23 · 2014: 23 · 2013: 23 · 2012: 28
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institute on Drug Abuse (DA 05274)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- bupropion, nicotinic acetylcholine receptors, nicotine antagonism, nicotine dependence, alpha4beta2 nicotinic receptor, alpha7 nicotinic acetylcholine receptor, antidepressants
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Male, Mice, Inbred ICR, Motor Activity, Nicotine, Receptors, Nicotinic, Bupropion, Nicotinic Antagonists, Mice
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