Anxiolytic-like effects of the novel cholinergic channel activator ABT-418
Abstract
The hydrochloride salt of (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT-418), a potent activator of select subtypes of neuronal nicotinic acetylcholine receptors enhanced retention in memory tests and induced anxiolytic-like effects in mice in the elevated plus maze. In the present studies in rats, ABT-418 induced a significant increase in the time spent by the rats in the open arms of the elevated plus maze (0.62 mumol/kg i.p.); the effect persisted up to 60 min after the injection and was blocked by mecamylamine (15 mumol/kg), a centrally acting nicotinic acetylcholine receptor channel blocker. ABT-418 was 6-fold and 1.6-fold more potent than diazepam and ondansetron, respectively. The anxiolytic-like effect of ABT-418 was observed after oral administration in rats (10-30 mumol/kg) and at slightly higher doses in 20-month-old rats (1.9 mumol/kg i.p.). Major metabolites of ABT-418 [(S)-1-methyl-5-(3-methyl-5-isoxazolyl)-2-pyrrolidinone, cis-ABT-418 N-oxide and trans-ABT-418 N-oxide] were inactive in the plus maze in mice up to 6.2 mumol/kg, did not affect body temperature and had minimal effects on locomotion. Like (-)-nicotine, ABT-418 was effective (4 and 13 mumol kg-1 day-1) to induce anxiolytic-like effects after a 14-day treatment through minipumps implanted subcutaneously. Acute administration of ABT-418 (0.62 mumol/kg i.p.) also attenuated the anxiogenic-like effect elicited by withdrawal from chronic (-)-nicotine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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The anxiolytic effects of ABT-418 were reversed by the nAChR antagonist mecamylamine.
“Brioni et al. (1994) also showed that the anxiolytic effects of ABT-418 were reversed by the nAChR antagonist mecamylamine”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Brioni et al. (1994)
The α4β2 nAChR agonist ABT-418 increased open arm time in the elevated plus maze, and both ABT-418 and the α4β2 partial agonist ABT-089 reversed the anxiogenic effects of nicotine withdrawal.
“an α4β2 nAChR agonist, ABT-418, was found to increase open arm time in the EPM and both ABT-418 and an α4β2 nAChR partial agonist, ABT-089, reversed the anxiogenic effects of nicotine withdrawal (Brioni et al., 1994; Decker et al., 1994; Yohn, Turner, & Blendy, 2014).”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Brioni et al., 1994
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- Authors
- Brioni, J. D., O'Neill, A. B., Kim, D. J., Buckley, M. J., Decker, M. W., & Arneric, S. P.
- Affiliations
- Abbott (United States) (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1994-10
- Volume
- 271
- Issue
- 1
- Pages
- 353-361
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1767734194
- Cited by
- 77
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2016: 1 · 2015: 4 · 2013: 1 · 2012: 2
- FWCI
- 2.26
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ABT-418, anxiolytic-like effects, nicotinic acetylcholine receptors, elevated plus maze, mecamylamine, nicotine, nicotine withdrawal, metabolites, isoxazole derivatives, anxiogenic effects
- MeSH terms
- Administration, Oral, Animals, Cognition Disorders, Diazepam, Isoxazoles, Male, Mecamylamine, Nicotine, Pyrrolidines, Substance Withdrawal Syndrome, Anti-Anxiety Agents, Rats, Wistar, Maze Learning, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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