CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity

Neuropharmacology. 2007 Feb;52(2):279-90. doi: 10.1016/j.neuropharm.2006.07.024. Epub 2006 Sep 1.


CP-809,101 is a potent, functionally selective 5-HT(2C) agonist that displays approximately 100% efficacy in vitro. The aim of the present studies was to assess the efficacy of a selective 5-HT(2C) agonist in animal models predictive of antipsychotic-like efficacy and side-effect liability. Similar to currently available antipsychotic drugs, CP-809,101 dose-dependently inhibited conditioned avoidance responding (CAR, ED(50)=4.8 mg/kg, sc). The efficacy of CP-809,101 in CAR was completely antagonized by the concurrent administration of the 5-HT(2C) receptor antagonist, SB-224,282. CP-809,101 antagonized both PCP- and d-amphetamine-induced hyperactivity with ED(50) values of 2.4 and 2.9 mg/kg (sc), respectively and also reversed an apomorphine induced-deficit in prepulse inhibition. At doses up to 56 mg/kg, CP-809,101 did not produce catalepsy. Thus, the present results demonstrate that the 5-HT(2C) agonist, CP-809,101, has a pharmacological profile similar to that of the atypical antipsychotics with low extrapyramidal symptom liability. CP-809,101 was inactive in two animal models of antidepressant-like activity, the forced swim test and learned helplessness. However, CP-809,101 was active in novel object recognition, an animal model of cognitive function. These data suggest that 5-HT(2C) agonists may be a novel approach in the treatment of psychosis as well as for the improvement of cognitive dysfunction associated with schizophrenia.

MeSH terms

  • Amphetamines
  • Animals
  • Antipsychotic Agents / chemistry
  • Antipsychotic Agents / therapeutic use*
  • Avoidance Learning / drug effects
  • Behavior, Animal
  • Catalepsy / chemically induced
  • Catalepsy / drug therapy
  • Dextroamphetamine
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Helplessness, Learned
  • Humans
  • Hyperkinesis / chemically induced
  • Hyperkinesis / drug therapy
  • Inhibition, Psychological
  • Male
  • Mice
  • Motor Activity / drug effects
  • NIH 3T3 Cells
  • Piperazines / chemistry
  • Piperazines / therapeutic use
  • Protein Binding / drug effects
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / etiology
  • Psychotic Disorders / physiopathology
  • Pyrazines / chemistry
  • Pyrazines / therapeutic use
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2C / physiology
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Receptor Agonists / therapeutic use*


  • Amphetamines
  • Antipsychotic Agents
  • CP-809,101
  • Piperazines
  • Pyrazines
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Receptor Agonists
  • 4-iodo-2,5-dimethoxyphenylisopropylamine
  • Dextroamphetamine