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Results from animal studies have suggested that serotonin (5-HT) antagonists acting on the 5-HT3 receptor may have anxiolytic properties. We have assessed whether pretreatment with the 5-HT3 receptor antagonist BRL 46470 (1 mg orally) attenuates the increase in anxiety induced in healthy volunteers by intravenous infusion of m-chlorophenylpiperazine (mCPP: 0.08 mg/kg over 2 min). In this double-blind placebo-controlled crossover study in 12 healthy men who were volunteers, infusion of mCPP caused significant increases in self-ratings for the psychological and physical symptoms of anxiety, for the symptoms of panic attack, and in the plasma levels of cortisol and prolactin, with four subjects (33%) experiencing an mCPP-induced "panic attack." Pretreatment with BRL 46470 did not attenuate any of these mCPP-induced changes. These results do not support suggestions from animal studies that 5-HT3 receptor antagonists can attenuate mCPP-induced anxiety, although it is conceivable that a different dose of BRL 46470 may have been effective.


Journal article


Biol Psychiatry

Publication Date





309 - 316


Administration, Oral, Adolescent, Adult, Anti-Anxiety Agents, Anxiety, Brain, Bridged Bicyclo Compounds, Bridged Bicyclo Compounds, Heterocyclic, Cross-Over Studies, Double-Blind Method, Humans, Hydrocortisone, Indoles, Infusions, Intravenous, Male, Middle Aged, Panic, Piperazines, Premedication, Prolactin, Receptors, Serotonin, Serotonin Antagonists, Serotonin Receptor Agonists