Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine
Abstract
Nicotinic acetylcholine receptors (nAChR) are diverse members of the neurotransmitter-gated ion channel superfamily and play critical roles in chemical signaling throughout the nervous system. The present study establishes the acute functional effects of bupropion, phencyclidine, and ibogaine on two human nAChR subtypes. Function of muscle-type nAChR (alpha1 beta gamma delta) in TE671/RD cells or of ganglionic nAChR (alpha3 beta4 alpha5+/-beta2) in SH-SY5Y neuroblastoma cells was measured with 86Rb+ efflux assays. Functional blockade of human muscle-type and ganglionic nAChR is produced by each of the drugs in the low to intermediate micromolar range. Functional blockade is insurmountable by increasing agonist concentrations in TE671/RD and SH-SY5Y cells for each of these drugs, suggesting noncompetitive inhibition of nAChR function. Based on these findings, we hypothesize that nAChR are targets of diverse substances of abuse and agents used in antiaddiction/smoking cessation strategies. We also hypothesize that nAChR play heretofore underappreciated roles in depression and as targets for clinically useful antidepressants.
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Three trials directly comparing bupropion and nortriptyline showed no significant differences, and the pooled odds ratio, though favouring bupropion, was non-significant (OR 1.4, 95% CI 0.9 to 2.3).
“Three trials have directly compared bupropion and nortriptyline (98–100). None showed significant differences and the pooled odds ratio, though favouring bupropion, was non significant (OR 1.4, 95% CI 0.9, 2.3).”
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- Authors
- Fryer, J. D., & Lukas, R. J.
- Affiliations
- Barrow Neurological Institute (US)
- St. Joseph's Hospital and Medical Center (US)
- ORCID
- Fryer, John D.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 288
- Issue
- 1
- Pages
- 88-92
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1912050742
- Cited by
- 283
- References
- 28
- Citations by year
- 2026: 2 · 2023: 7 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 10 · 2014: 8 · 2013: 9 · 2012: 14
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- 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
- nicotinic acetylcholine receptors, non-competitive inhibition, bupropion, phencyclidine, ibogaine, muscle-type nAChR, 86Rb efflux, SH-SY5Y cells, smoking cessation, antidepressant targets, depression, substance abuse
- MeSH terms
- Antidepressive Agents, Cell Line, Humans, Ibogaine, Phencyclidine, Receptors, Nicotinic, Tumor Cells, Cultured, Bupropion, Excitatory Amino Acid Antagonists, Dopamine Uptake Inhibitors
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