ArticlePsychopharmacology2014
Discriminative stimulus and hypothermic effects of some derivatives of the nAChR agonist epibatidine in mice.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Stimulus mediation, specificity and impact of menthol in rats trained to discriminate puffs of nicotine e-cigarette aerosol from nicotine-free aerosol.Psychopharmacology · 2024Article
- Evaluation of novel epibatidine analogs in the rat nicotine drug discrimination assay and in the rat chronic constriction injury neuropathic pain model.Advances in drug and alcohol research · 2023Article
- Nicotinic Acetylcholine Receptor Accessory Subunits Determine the Activity Profile of Epibatidine Derivatives.Molecular pharmacology · 2020Article
- The discriminative stimulus effects of epibatidine in C57BL/6J mice.Behavioural pharmacology · 2020Article
- Unexpected loss of sensitivity to the nicotinic acetylcholine receptor antagonist activity of mecamylamine and dihydro-β-erythroidine in nicotine-tolerant mice.Brain and behavior · 2020Article
- Enhancement of Opioid Antinociception by Nicotine.The Journal of pharmacology and experimental therapeutics · 2019Article
- Differential cross-tolerance to the effects of nicotinic acetylcholine receptor drugs in C57BL/6J mice following chronic varenicline.Behavioural pharmacology · 2019Article
- Rapid nicotine tolerance and cross-tolerance to varenicline in rhesus monkeys: Drug discrimination.Experimental and clinical psychopharmacology · 2018Article
- The discriminative stimulus effects of i.v. nicotine in rhesus monkeys: Pharmacokinetics and apparent pANeuropharmacology · 2017Article
- Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily.British journal of pharmacology · 2016Article
- Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice.European journal of pharmacology · 2016Article
- Differential antagonism and tolerance/cross-tolerance among nicotinic acetylcholine receptor agonists: scheduled-controlled responding and hypothermia in C57BL/6J mice.Behavioural pharmacology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleReceptor mechanisms underlying the in vivo effects of nicotinic acetylcholine receptor (nAChR) drugs need to be determined to better understand possible differences in therapeutic potential.
objectiveThis study compared the effects of agonists that are reported either to differ in intrinsic activity (i.e., efficacy) at α4β2 nAChR in vitro or to have in vivo effects consistent with differences in efficacy. The drugs included nicotine, varenicline, cytisine, epibatidine, and three novel epibatidine derivatives: 2'-fluoro-3'-(4-nitrophenyl)deschloroepibatidine (RTI-7527-102), 2'-fluorodeschloroepibatidine (RTI-7527-36), and 3'-(3″-dimethylaminophenyl)-epibatidine (RTI-7527-76).
methodsMice discriminated nicotine base (1 mg/kg base) from saline; other mice were used to measure rectal temperature.
resultsIn the nicotine discrimination assay, the maximum percentage of nicotine-appropriate responding varied: 92 % for nicotine, 84 % for epibatidine, 77 % for RTI-7527-36, and 71 % for varenicline and significantly less for RTI-7527-76 (58 %), RTI-7527-102 (46 %), and cytisine (33 %). Each drug markedly decreased rectal temperature by as much as 12 ºC. The rank-order potency in the discrimination and hypothermia assays was epibatidine > RTI-7527-36 > nicotine > RTI-7527-102 > varenicline = cytisine = RTI-7527-76. The nAChR antagonist mecamylamine (3.2 mg/kg) antagonized the discriminative stimulus effects of epibatidine and RTI-7527-102, as well as the hypothermic effects of every drug except cytisine. The β2-subunit selective nAChR antagonist dihydro-β-erythroidine (DHβE; up to 10 mg/kg) antagonized hypothermic effects but less effectively so than mecamylamine.
conclusionsThe marked hypothermic effects of all drugs except cytisine are due in part to agonism at nAChR containing β2-subunits. Differential substitution for the nicotine discriminative stimulus is consistent with differences in α4β2 nAChR efficacy; however, collectively the current results suggest that multiple nAChR receptor subtypes mediate the effects of the agonists.
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Registered trials
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