Ritanserin antagonism of m-chlorophenylpiperazine effects in neuroleptic-free schizophrenics patients: support for serotonin-2 receptor modulation of schizophrenia symptoms.
BACKGROUND
Serotonin-2 (5-HT(2)) receptor antagonism has been hypothesized to have antipsychotic activity. However, there has been limited evidence directly linking 5-HT(2) receptor antagonism to symptom control in schizophrenic patients.


OBJECTIVE
In order to test this hypothesis this study evaluated the capacity of pretreatment with the 5-HT(2) receptor antagonist ritanserin to attenuate the effects of the 5-HT agonist, m-chlorophenylpiperazine (mCPP).


METHODS
Twenty-two male inpatients who met DSM-III-R criteria for schizophrenia or schizoaffective disorder completed 4 test days during which 10 mg ritanserin or matched placebo was administered orally 50 min prior to the intravenous infusion of 0.1 mg/kg mCPP or saline. The test days were conducted in a randomized order under double-blind conditions.


RESULTS
mCPP mildly and transiently increased positive symptoms and behavioral activation but not negative symptoms, as assessed by the Brief Psychiatric Rating Scale. mCPP also raised plasma prolactin and cortisol levels. All of these effects were attenuated by ritanserin pretreatment.


CONCLUSIONS
These data support a contribution of 5-HT(2) receptor stimulation to symptom exacerbation in schizophrenic patients and a role for 5-HT(2) receptor antagonism in the prevention of this effect.
Abi-Saab
Walid
W
Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. 06519 , USA.
Seibyl
John P
JP
D'Souza
D Cyril
DC
Karper
Laurence P
LP
Gueorgueva
Ralitza
R
Abi-Dargham
Anissa
A
Wong
Ma-Li
ML
Rajhans
Sachin
S
Erdos
Joseph P
JP
Heninger
George R
GR
Charney
Dennis S
DS
Krystal
John H
JH
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011985:Receptors, Serotonin / Q000502:physiology*; D012044:Regression Analysis; D016713:Ritanserin / Q000494:pharmacology* / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D014150:Antipsychotic Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; C015068:1-(3-chlorophenyl)piperazine