ArticleChemMedChem2009
Chemistry and pharmacology of nicotinic ligands based on 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol (AMOP-H-OH) for possible use in depression.
Article in ChemMedChem, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- α4β2 Nicotinic receptor desensitizing compounds can decrease self-administration of cocaine and methamphetamine in rats.European journal of pharmacology · 2019Article
- Roles of nicotinic acetylcholine receptor β subunit cytoplasmic loops in acute desensitization and single-channel features.Neuroscience · 2015Article
- Enantiopure Cyclopropane-Bearing Pyridyldiazabicyclo[3.3.0]octanes as Selective α4β2-nAChR Ligands.ACS medicinal chemistry letters · 2014Article
- Recent developments in novel antidepressants targeting α4β2-nicotinic acetylcholine receptors.Journal of medicinal chemistry · 2014Review
- The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain: biochemical and pharmacological characterization.Molecular pharmacology · 2014Article
- Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain.Journal of neurochemistry · 2014Article
- The unique α4+/-α4 agonist binding site in (α4)3(β2)2 subtype nicotinic acetylcholine receptors permits differential agonist desensitization pharmacology versus the (α4)2(β2)3 subtype.The Journal of pharmacology and experimental therapeutics · 2014Article
- Cognition as a therapeutic target in late-life depression: potential for nicotinic therapeutics.Biochemical pharmacology · 2013Review
- Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Article
- Chemistry and pharmacological studies of 3-alkoxy-2,5-disubstituted-pyridinyl compounds as novel selective α4β2 nicotinic acetylcholine receptor ligands that reduce alcohol intake in rats.Journal of medicinal chemistry · 2013Article
- Acute activation, desensitization and smoldering activation of human acetylcholine receptors.PloS one · 2013Article
- A new radioligand binding assay to measure the concentration of drugs in rodent brain ex vivo.The Journal of pharmacology and experimental therapeutics · 2012Article
- Chronic sazetidine-A at behaviorally active doses does not increase nicotinic cholinergic receptors in rodent brain.The Journal of pharmacology and experimental therapeutics · 2012Article
- Insights into the structural determinants required for high-affinity binding of chiral cyclopropane-containing ligands to α4β2-nicotinic acetylcholine receptors: an integrated approach to behaviorally active nicotinic ligands.Journal of medicinal chemistry · 2012Article
- Effects of sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, on body temperature regulation in mice and rats.European journal of pharmacology · 2012Article
- Chemistry and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile.Journal of medicinal chemistry · 2012Article
- The nicotinic acetylcholine receptor as a target for antidepressant drug development.TheScientificWorldJournal · 2012Review
- Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression.Journal of medicinal chemistry · 2011Article
- Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380.Psychopharmacology · 2011Article
- Chemistry and pharmacological characterization of novel nitrogen analogues of AMOP-H-OH (Sazetidine-A, 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol) as α4β2-nicotinic acetylcholine receptor-selective partial agonists.Journal of medicinal chemistry · 2010Article
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11 authors at 3 institutions in 1 country.
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Abstract
AMOP-H-OH (sazetidine-A; 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol) and some sulfur-bearing analogues were tested for their activities in vitro against human alpha4beta2-, alpha4beta4-, alpha3beta4*- and alpha1*-nicotinic acetylcholine receptors (nAChRs). AMOP-H-OH was also assessed in an antidepressant efficacy model. AMOP-H-OH and some of its analogues have high potency and selectivity for alpha4beta2-nAChRs over other nAChR subtypes. Effects are manifested as partial agonism, perhaps reflecting selectivity for high sensitivity (alpha4)(3)(beta2)(2)-nAChRs. More prolonged exposure to AMOP-H-OH and its analogues produces inhibition of subsequent responses to acute challenges with full nicotinic agonists, again selectively for alpha4beta2-nAChRs over other nAChR subtypes. The inhibition is mediated either via antagonism or desensitization of nAChR function, but the degree of inhibition of alpha4beta2-nAChRs is limited by the partial agonist activity of the drugs. Certain aspects of the in vitro pharmacology suggest that AMOP-H-OH and some of its analogues have a set of binding sites on alpha4beta2-nAChRs that are distinct from those for full agonists. The in vitro pharmacological profile suggests that peripheral side effects of AMOP-H-OH or its analogues would be minimal and that their behavioral effects would be dominated by central nAChR actions. AMOP-H-OH also has profound and high potency antidepressant-like effects in the forced swim test. The net action of prolonged exposure to AMOP-H-OH or its analogues, as for nicotine, seems to be a selective decrease in alpha4beta2-nAChR function. Inactivation of nAChRs may be a common neurochemical endpoint for nicotine dependence, its treatment, and some of its manifestations, including relief from depression.
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