NE-100, a novel sigma receptor ligand: in vivo tests.
It has been suggested that sigma receptor antagonists may be useful as antipsychotic drugs. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) is a novel compound with high affinity for the sigma receptor (IC50 = 4.16 nM), but low affinity (IC50 > 10,000 nM) for D1, D2, 5-HT1A, 5-HT2 and phencyclidine (PCP) receptors. The head-weaving behavior induced by either (+)SKF10047 or PCP was dose-dependently antagonized by NE-100 with oral ED50 at 0.27 and 0.12 mg/kg, respectively. NE-100 did not affect dopamine agonists-induced stereotyped behavior and/or hyperactivity. NE-100 failed to induce catalepsy in rats. These findings indicate that NE-100 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics.
Okuyama
S
S
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Imagawa
Y
Y
Ogawa
S
S
Araki
H
H
Ajima
A
A
Tanaka
M
M
Muramatsu
M
M
Nakazato
A
A
Yamaguchi
K
K
Yoshida
M
M
D000818:Animals; D000840:Anisoles / Q000378:metabolism / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D002375:Catalepsy / Q000139:chemically induced; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011437:Propylamines / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*; D013239:Stereotyped Behavior / Q000187:drug effects
D000840:Anisoles; D014150:Antipsychotic Agents; D015259:Dopamine Agents; D011437:Propylamines; D017480:Receptors, sigma; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine