Dopamine D1 (SCH 23390) and D2 (haloperidol) antagonists in drug-naive monkeys.
Dopamine D1 (SCH 23390) and D2 (haloperidol) antagonists in drug-naive monkeys.
复制标题
未接触过药物的猴子体内的多巴胺 D1 (SCH 23390) 和 D2（氟哌啶醇）拮抗剂。
DOI：
10.1007/bf02244960
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发表时间：
1992
影响因子：
3.4
通讯作者：
Casey,DE
中科院分区：
文献类型：
--
作者：
Casey,DE
多巴胺D1拮抗剂在非人灵长类动物中产生急性锥体外系综合征（EPS）的能力尚不清楚。在猴子中的一些研究表明，D1拮抗剂产生急性肌张力障碍，而其他研究没有报告这些影响。产生矛盾结果的中心问题围绕着既往治疗状态（未使用过抗精神病药物与致敏的抗精神病药物）和给药途径（口服与胃肠外）。在本研究中，对单独的抗精神病药物初治猕猴组每周一次肌内注射SCH 23390（一种D1拮抗剂）或氟哌啶醇（一种D2拮抗剂）（剂量范围为0.01-0.25 mg/kg）和生理盐水对照。两种活性药物，而不是生理盐水，产生临床上相同的急性肌张力障碍和运动迟缓综合征，虽然氟哌啶醇诱导更高的症状评分在较长的时间。SCH 23390的镇静作用和运动活动没有变化，但氟哌啶醇的镇静作用和运动活动有所下降。关于急性EPS的非人灵长类动物模型和临床意义的影响因素进行了讨论。
The ability of dopamine D1antagonists to produce acute extrapyramidal syndromes (EPS) in nonhuman primates is unclear. Some studies in monkeys show that D1antagonists produce acute dystonia, whereas other studies do not report these effects. The central issues that have yielded conflicting results revolve around prior treatment status (neuroleptic-naive versus neuroleptic sensitized) and route of administration (oral versus parenteral). In this study, separate groups of neuroleptic drug-naive cebus monkeys were tested once weekly with intramuscularly administered SCH 23390, a D1antagonist, or haloperidol, a D2antagonist, across a dose range of 0.01–0.25 mg/kg, and a saline control. Both active drugs, but not saline, produced clinically identical syndromes of acute dystonia and bradykinesia, though haloperidol induced higher symptom scores over a longer duration. Sedation and locomotor activity were unchanged by SCH 23390, but decreased with haloperidol. Factors regarding acute EPS liability in nonhuman primate models and clinical implications in man are discussed.