海马多巴胺（DA）受体阻断：一种用于具有低锥体外系副作用的抗精神病药物的工具。

Blockade of hippocampal dopamine (DA) receptors: a tool for antipsychotics with low extrapyramidal side effects.

Bischoff S, Christen P, Vassout A

Pharma. Research Department, Ciba-Geigy Ltd., Basle, Switzerland.

Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(4):455-67. doi: 10.1016/0278-5846(88)90105-4.

Abstract

32 neuroleptics (NL) and a Ciba-Geigy antipsychotic (savoxepine, CGP 19 486 A) were tested on adult male rats and mice. 2. Interaction with D2 DA receptors was assessed using in vivo (3H)spiperone (SPI) binding in rat hippocampus and striatum. 3. Antipsychotic efficacy of NL was checked by their ability to antagonize apomorphine-induced climbing behavior in mice. 4. We found a good correlation between blockade of DA receptors in hippocampus and antagonism of climbing with both classical and atypical NL. 5. No correlation was found between blockade of DA receptors in striatum and climbing with the atypical NL. 6. It is suggested that NL exerting preferential blockade of hippocampal as compared to striatal DA receptors may show a better dissociation between antipsychotic efficacy and induction of extrapyramidal side effects (EPS) in the clinic. The antipsychotic agent savoxepine, displayed such a favourable profile of action.

摘要

对成年雄性大鼠和小鼠测试了32种抗精神病药物（NL）以及一种汽巴 - 嘉基公司的抗精神病药（沙沃昔平，CGP 19486 A）。2. 使用大鼠海马体和纹状体中的体内（3H）司哌罗宁（SPI）结合来评估与D2多巴胺受体的相互作用。3. 通过NL拮抗小鼠阿扑吗啡诱导的攀爬行为的能力来检查其抗精神病疗效。4. 我们发现，经典和非典型NL在海马体中对多巴胺受体的阻断与对攀爬行为的拮抗作用之间存在良好的相关性。5. 在纹状体中对多巴胺受体的阻断与非典型NL的攀爬行为之间未发现相关性。6. 有人提出，与纹状体多巴胺受体相比，对海马体多巴胺受体具有优先阻断作用的NL在临床上可能在抗精神病疗效和锥体外系副作用（EPS）诱导之间表现出更好的分离。抗精神病药物沙沃昔平表现出这样有利的作用特征。