The 5-HT3 antagonist, BRL 46470 does not attenuate m-chlorophenylpiperazine (mCPP)-induced changes in human volunteers.
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.
Silverstone
P H
PH
MRC Unit of Clinical Pharmacology, Littlemore Hospital, Oxford, U.K.
Cowen
P J
PJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007211:Indoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010200:Panic / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011292:Premedication; D011388:Prolactin / Q000097:blood; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C075685:BRL 46470; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine; D006854:Hydrocortisone