Effects of sigma(1) receptor ligand, MS-377 on apomorphine- or phencyclidine-induced disruption of prepulse inhibition of acoustic startle in rats.
To evaluate the antipsychotic property of a sigma(1) receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-¿4-(2-methoxyethyl)piperazin-1-yl¿ methyl-2-pyrrolidinone-L-tartrate (MS-377), an antagonistic effect of MS-377 on the disruption of prepulse inhibition (PPI) of the acoustic startle by apomorphine or phencyclidine (PCP) was investigated in rats. MS-377 antagonized the PCP-induced disruption of PPI. The ED(50) value of MS-377 for this effect was 0.66 mg/kg. In contrast, apomorphine-induced disruption of PPI was not attenuated by MS-377. These data indicate that the PCP-induced disruption of PPI in rats would be, at least partially, mediated by sigma receptors and MS-377 could be a novel anti-psychotic agent with clinical efficacy for the sensorimotor-gating deficit in schizophrenia.
Yamada
S
S
Institute of Brain Diseases, Kurume University School of Medicine, 67 Asahi Machi, 830-0011, Kurume, Japan. shyamada@med.kurume-u.ac.jp
Yamauchi
K
K
Hisatomi
S
S
Annoh
N
N
Tanaka
M
M
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*; D013644:Tartrates; D000097605:Sigma-1 Receptor
D006916:5-Hydroxytryptophan; D014150:Antipsychotic Agents; D001058:Apomorphine; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine; D010879:Piperazines; D011759:Pyrrolidines; D017480:Receptors, sigma; D013644:Tartrates; D000097605:Sigma-1 Receptor; C464615:1-(4-chlorophenyl)-3-(4-(2-methoxyethyl) piperazin-1-yl)methyl-2-pyrrolidinone tartrate