SIGMA-OPIATES AND CERTAIN ANTIPSYCHOTIC-DRUGS MUTUALLY INHIBIT (+)-[H-3]SKF-10,047 AND [H-3]HALOPERIDOL BINDING IN GUINEA-PIG BRAIN MEMBRANES
SIGMA-OPIATES AND CERTAIN ANTIPSYCHOTIC-DRUGS MUTUALLY INHIBIT (+)-[H-3]SKF-10,047 AND [H-3]HALOPERIDOL BINDING IN GUINEA-PIG BRAIN MEMBRANES
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DOI：
10.1073/pnas.81.17.5618
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
COOK, L
中科院分区：
文献类型：
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作者：
TAM, SW;COOK, L
抗精神病药物的结合与σ的关系。抗精神病的阿片类药物与西格玛的结合部位。研究了激动剂(+)-[~3H]SKF 10,047(N-烯丙基去甲恶唑碱)和多巴胺D2位点。在豚鼠脑膜上，(+)-[~3H]SKF 10,047与一类部位结合，Kd为4倍。10-8M，Bmax为333fmol/mg蛋白质。此结合不同于MU、KAPPA.或Delta。阿片受体结合。它被产生拟精神活动的阿片剂抑制，但不被缺乏这种活动的阿片剂抑制。一些抗精神病药物以高到中等亲和力抑制(+)-[~3H]SKF 10,047的结合，其效力顺序如下：氟哌啶醇和GT；奋乃静和GT；氟吩嗪和GT；苯吩嗪和GT；三氟拉嗪和喹诺酮。匹莫齐德。gtoreq。硫代咪嗪.gtoreq.氯丙嗪。gtoreq。三氟丙嗪。还有其他抗精神病药物，如Speperone和氯氮平，对(+)-[~3H]SKF 10,047个结合位点显示低亲和力。抗精神病药物与(+)-[~3H]SKF 10,047结合位点的亲和力与与[~3H]螺环酮(多巴胺D2)结合位点的亲和力无关。[~3H]-氟哌啶醇在全脑膜上的结合也被Sigma抑制。鸦片类药物五唑类、环氮唑类和(+)-SKF 10,047。在纹状体，约一半可饱和的[~3H]氟哌啶醇结合到[~3H]螺环酮(D2)部位，另一半与类似于(+)-[~H]SKF 10,047个结合部位。
The relationship between binding of antipsychotic drugs and .sigma. psychotomimetic opiates to binding sites for the .sigma. agonist (+)-[3H]SKF 10,047 (N-allylnormetazocine) and to dopamine D2 sites was investigated. In guinea pig brain membranes, (+)-[3H]SKF 10,047 bound to a single class of sites with a Kd of 4 .times. 10-8 M and Bmax of 333 fmol/mg of protein. This binding was different from .mu., .KAPPA., or .delta. opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[3H]SKF 10,047 binding with high to moderate affinities in the following order of potency:haloperidol > perphenazine > fluphenazine > acetophenazine > trifluoperazine > molindone .gtoreq. pimozide .gtoreq. thioridazine .gtoreq. chlorpromazine .gtoreq. triflupromazine. There were other antipsychotic drugs such as speperone and clozapine that showed low affinity for the (+)-[3H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[3H]SKF 10,047 binding sites did not correlate with those for [3H]spiperone (dopamine D2) sites. [3H]-Haloperidol binding in whole brain membranes was also inhibited by the .sigma. opiates pentazocine, cyclazocine and (+)-SKF 10,047. In the striatum, about half of the saturable [3H]haloperidol binding was to [3H]spiperone (D2) sites and the other half was to sites similar to (+)-[3H]SKF 10,047 binding sites.