Effects of a novel, selective, sigma(1)-ligand, MS-377, on phencyclidine-induced behaviour

Phencyclidine (PCP)-induced head-weaving is inhibited by a novel selective sigma (1)-ligand, (R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin -1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377), but not by dopamine D, an tagonists. In the present study, we examined the effects of two potent and selective sigma (1)-ligands, MS-377 and N,N-dipropyl-2-(4-methoxy-3-(2-phen yleth ethylamine (NE-100), on PCP-induced rearing behaviour, hyperlocomotio n and ataxia in comparison with the currently available antipsychotic agent s with affinity for D-2 receptors, haloperidol, sultopride and risperidone. Male Wistar rats or ddY mice were administered MS-377, NE-100, haloperidol , sultopride or risperidone, and PCP was administered 60 min later tin the case of NE-100 10 min later). Rearing behaviour, hyperlocomotion and ataxia were examined 10 min after PCP administration. MS-377, haloperidol, sultop ride and risperidone dose-dependently inhibited PCP-induced rearing and hyp erlocomotion, but did not antagonize PCP-induced ataxia. In contrast, the o ther selective sigma (1)-ligand, NE-100, did not affect any of the PCP-indu ced behaviour patterns in this study. These results suggest that there are at least two types of ligands for ol-receptors and that some sigma (1)-liga nds, including MS-377, have more comprehensive effects against PCP-induced abnormal behaviour than other sigma (1)-ligands or D-2 antagonists.