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.