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-pyrroli dinone-L-tartrate (MS-377), an antagonistic effect of MS-377 on the disrupt ion of prepulse inhibition (PPI) of the acoustic startle by apomorphine or phencyclidine (PCP) was investigated in rats. MS-377 antagonized the PCP-in duced disruption of PPI. The ED50 value of MS-377 for this effect was 0.66 mg/kg. In contrast, apomorphine-induced disruption of PPI was not attenuate d 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 c ould be a novel anti-psychotic agent with clinical efficacy for the sensori motor-gating deficit in schizophrenia. (C) 2000 Elsevier Science B.V. All r ights reserved.