Okuyama S, Imagawa Y, Ogawa S, Araki H, Ajima A, Tanaka M, Muramatsu M, Nakazato A, Yamaguchi K, Yoshida M
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Life Sci. 1993;53(18):PL285-90. doi: 10.1016/0024-3205(93)90588-t.
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.
有人提出，σ受体拮抗剂可能作为抗精神病药物有用。N，N-二丙基-2-[4-甲氧基-3-(2-苯乙氧基)苯基]-乙胺盐酸盐（NE-100）是一种对σ受体具有高亲和力（IC50 = 4.16 nM），但对D1、D2、5-HT1A、5-HT2和苯环己哌啶（PCP）受体具有低亲和力（IC50 > 10,000 nM）的新型化合物。由(+)SKF10047或PCP诱导的头部摆动行为被NE-100剂量依赖性拮抗，口服ED50分别为0.27和0.12 mg/kg。NE-100不影响多巴胺激动剂诱导的刻板行为和/或多动。NE-100未能在大鼠中诱导僵住症。这些发现表明，NE-100可能具有抗精神病活性，而没有典型抗精神病药物的运动副作用倾向。
