The 5-HT3 antagonist, BRL 46470 does not attenuate m-chlorophenylpiperazine (mCPP)-induced changes in human volunteers.

Journal article

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.

Authors: Silverstone, P; Cowen, P

• Publication status: Published
• Journal: Biological psychiatry
• Volume: 36
• Issue: 5
• Pages: 309-316
• Publication date: 1994-09-01
• DOI: 10.1016/0006-3223(94)90628-9
• EISSN: 1873-2402
• ISSN: 0006-3223
• Language: English
• Keywords: Bicyclo Compounds, Heterocyclic; Male; Premedication; Serotonin Antagonists; Indoles; Administration, Oral; Hydrocortisone; Bicyclo Compounds; Infusions, Intravenous; Double-Blind Method; Prolactin; Anti-Anxiety Agents; Receptors, Serotonin; Adolescent; Humans; Middle Aged; Adult; Panic; Anxiety; Piperazines; Serotonin Receptor Agonists; Cross-Over Studies; Brain