Atypical antipsychotic profiles of dopamine D_4 receptor antagonist, (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-(4-(4-fluorophenyl)-4-oxobutyl)pyrrolidine-3-yl]thiazole (NRA0045) in Rats

NRA0045 is a potent dopamine D_4 and serotonin (5-HT)_2A receptor antagonist. Phencyclidine (PCP) elicits predominantly psychotic symptoms in normal humans and in schizophrenics. NAR0045 and clozapine significantly and dose-dependently shortened the phencyclidine (PCP)-induced prolonged swimming lat...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1997, Vol.73 (suppl.2), p.243-243
Main Authors: Shin-ichi Ogawa, Shigeru Okuyama, Yoshiko Suzuki, Shigeyuki Chaki, Toshihito Kumagai, Atsuro Nakazato, Yoko Ikeda, Masashi Nagamine, Makoto Gotoh, Masanori Yoshida, Kazuyuki Tomisawa
Format: Article
Language:Japanese
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Summary:NRA0045 is a potent dopamine D_4 and serotonin (5-HT)_2A receptor antagonist. Phencyclidine (PCP) elicits predominantly psychotic symptoms in normal humans and in schizophrenics. NAR0045 and clozapine significantly and dose-dependently shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task, whereas swimming latency after haloperidol administration did not differ from that seen in the PCP-treated group. Prepulse inhibition (PPI) is markedly impaired in humans with schizophrenia. The disruption of prepulse PPI in rats by apomorphine (0.5 mg/kg, s.c.) is significantly reversed by NRA0045, clozapine and haloperidol. These findings indicate NRA0045 may have a unique antipsychotic activity in experimental animals.
ISSN:0021-5198