Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phencylidine (PCP) is a psychotomimetic noncompetitive glutamate antagonist that has been used in studies of the neural substrates of psychosis. Both schizophrenic patients and PCP-treated rats exhibit reduced amounts of prepulse inhibition (PPI) of the startle reflex, which is the normal inhibition of startle that occurs when the starting noise is preceded 30 to 500 msec by a weak prepulse. The present study assessed the effects of seroquel (ICI 204,636), a mixed D2/5-hydroxytryptamine2 antagonist with a preclinical profile suggestive of potential antipsychotic efficacy, on the PCP-induced disruption of PPI. Clozapine, risperidone and haloperidol were also studied as comparison compounds. PCP (1.25 mg/kg) significantly reduced PPI, with prepulses that were 1 to 12 dB above background. Seroquel and clozapine significantly restored PPI in PCP-treated rats, whereas haloperidol and risperidone did not. Similar findings were obtained in studies using separate animals, a slightly lower dose of PCP (1.0 mg/kg) and a high dose of each of these antipsychotics. Separate studies verified that risperidone and haloperidol restored PPI in apomorphine-treated rats. In the present studies, seroquel exhibited a profile consistent with those exhibited by other "atypical" antipsychotics.
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PMID:Seroquel restores sensorimotor gating in phencyclidine-treated rats. 896 53

Schizophrenic and schizotypal patients exhibit deficits in the habituation and prepulse inhibition (PPI) of startle responses, providing operational measures of the sensorimotor gating or filtering deficits suggested to contribute to cognitive disorganization in these patients. In rats, hallucinogens, entactogens, and NMDA antagonists share the ability to both retard startle habituation and disrupt PPI. Extensive pharmacological studies in rats have indicated that the effects of hallucinogens on habituation are mediated by direct agonist actions at 5-HT2 receptors. The effects of the entactogens on both habituation and PPI reflect indirect agonist actions due to the stimulation of presynaptic serotonin release. These observations in rats have supported the development of 5-HT2A antagonists for the treatment of schizophrenia. Animal studies have shown that PPI is modulated by multiple interacting neurotransmitters, including dopaminergic, serotonergic, cholinergic, GABAergic, and glutamatergic systems within cortical, limbic, striatal, and brainstem structures. The effects of PCP and other NMDA antagonists on PPI are insensitive to either dopaminergic or serotonergic antagonists, but are reduced by atypical antipsychotics such as clozapine, olanzapine, and Seroquel. Thus, the PCP model of schizophrenia-like deficits in sensorimotor gating offers promise for the identification and neurobiological investigation of atypical antipsychotics. The cross-species study of homologous gating functions, such as habituation and PPI, in animal models and psychiatric patients provides novel opportunities for the exploration of neurobiological substrates relevant to the group of schizophrenias.
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PMID:Behavioral studies of hallucinogenic drugs in animals: implications for schizophrenia research. 975 37