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

Abstract

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.

• Authors: Judith A Siuciak, Douglas S Chapin, Sheryl A McCarthy, Victor Guanowsky, Janice Brown, Phoebe Chiang, Ravi Marala, Terrell Patterson, Patricia A Seymour, Andrew Swick, Philip A Iredale
• Journal: Neuropharmacology (Neuropharmacology) Vol. 52 Issue 2 Pg. 279-90 (Feb 2007) ISSN: 0028-3908 [Print] England
• PMID: 16949622 (Publication Type: Journal Article)

Chemical References

• 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

Topics

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