ArticlePsychopharmacology2008
S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models.
Article in Psychopharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 124 citations in OpenAlex.
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- A Subset of Purposeless Oral Movements Triggered by Dopaminergic Agonists Is Modulated by 5-HTInternational journal of molecular sciences · 2020Article
- Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain.Frontiers in pharmacology · 2020Article
- Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice.Pharmaceutical biology · 2016Article
- Altering the course of schizophrenia: progress and perspectives.Nature reviews. Drug discovery · 2016Review
- The effects of the dopamine stabilizer (-)-OSU6162 on aggressive and sexual behavior in rodents.Translational psychiatry · 2016Article
- Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models.British journal of pharmacology · 2016Article
- Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule.Psychopharmacology · 2015Article
- A Review of Biomarkers in Mood and Psychotic Disorders: A Dissection of Clinical vs. Preclinical Correlates.Current neuropharmacology · 2015Review
- GABAergic control of depression-related brain states.Advances in pharmacology (San Diego, Calif.) · 2015Article
- Adult neurogenesis and mental illness.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleSerotonin (5-HT)(2C) receptors are implicated in the control of mood, and their blockade is of potential interest for the management of anxiodepressive states.
objectivesHerein, we characterized the in vitro and in vivo pharmacological profile of the novel benzourea derivative, S32006. MATERIALS AND
methodsStandard cellular, electrophysiological, neurochemical, and behavioral procedures were used.
resultsS32006 displayed high affinity for human (h)5-HT(2C) and h5-HT(2B) receptors (pK (i)s, 8.4 and 8.0, respectively). By contrast, it had negligible (100-fold lower) affinity for h5-HT(2A) receptors and all other sites examined. In measures of Gq-protein coupling/phospholipase C activation, S32006 displayed potent antagonist properties at h5-HT(2C) receptors (pK (B) values, 8.8/8.2) and h5-HT(2B) receptors (7.8/7.7). In vivo, S32006 dose-dependently (2.5-40.0 mg/kg, i.p. and p.o.) abolished the induction of penile erections and a discriminative stimulus by the 5-HT(2C) receptor agonist, Ro60,0175, in rats. It elevated dialysis levels of noradrenaline and dopamine in the frontal cortex of freely moving rats, and accelerated the firing rate of ventrotegmental dopaminergic and locus ceruleus adrenergic neurons. At similar doses, S32006 decreased immobility in a forced-swim test in rats, reduced the motor depression elicited by 5-HT(2C) and alpha(2)-adrenoceptor agonists, and inhibited both aggressive and marble-burying behavior in mice. Supporting antidepressant properties, chronic (2-5 weeks) administration of S32006 suppressed "anhedonia" in a chronic mild stress procedure and increased both expression of BDNF and cell proliferation in rat dentate gyrus. Finally, S32006 (0.63-40 mg/kg, i.p. and p.o) displayed anxiolytic properties in Vogel conflict and social interaction tests in rats.
conclusionS32006 is a potent 5-HT(2C) receptor antagonist, and possesses antidepressant and anxiolytic properties in diverse rodent models.
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