NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys.
Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.
Okuyama
S
S
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Imagawa
Y
Y
Sakagawa
T
T
Nakazato
A
A
Yamaguchi
K
K
Katoh
M
M
Yamada
S
S
Araki
H
H
Otomo
S
S
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001259:Ataxia / Q000139:chemically induced; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004569:Electroencephalography; D005260:Female; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D010622:Phencyclidine; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects*; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy*
D000840:Anisoles; D008024:Ligands; D011437:Propylamines; D017480:Receptors, sigma; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; D010622:Phencyclidine