Costall B, Naylor R J
Psychopharmacologia. 1975 Jul 23;43(1):69-74. doi: 10.1007/BF00437617.
The cataleptic and antistereotypic abilities of clozapine, sulpiride and thioridazine were determined in the rat and compared with the responses of typical neuroleptic agents, haloperidol, fluphenazine and pimozide. Haloperidol and fluphenazine caused a dose-dependent cataleptic state which attained maximum intensity: the effects of pimozide were also dose-dependent but, although the catalepsy was marked, maximum intensity was not attained. In contrast, thioridazine, clozapine and sulpiride each caused a very weak, but definite, cataleptic response although a dose-dependency could not be demonstrated. Pretreatment of animals with alpha-methylparatyrosine was shown to significantly potentiate the cataleptic actions of haloperidol, fluphenazine, pimozide, thioridazine and sulpiride but failed to modify the action of clozapine, Threshold cataleptic doses of all agents markedly synergised in the production of catalepsy with threshold doses of the cholinergic drug RS86. Similarly, all "neuroleptic" agents tested were shown to reduce the intensity of the stereotyped behaviour induced by amphetamine, apomorphine and nomifensine in a dose-dependent manner but only haloperidol, fluphenazine and pimozide were shown to be capable of 100% inhibition. The antistereotypic abilities of haloperidol, fluphenazine and pimozide were most marked against amphetamine, but this was not a consistent observation for thioridazine, clozapine and sulpiride. Threshold, or even subthreshold, doses of both the typical and atypical neuroleptic agents combined with threshold doses of RS86 markedly synergised in the antagonism of the stereotypic actions of amphetamine, apomorphine and nomifensine.
在大鼠中测定了氯氮平、舒必利和硫利达嗪的僵住症及抗刻板行为能力，并与典型抗精神病药物氟哌啶醇、氟奋乃静和匹莫齐特的反应进行了比较。氟哌啶醇和氟奋乃静可引起剂量依赖性的僵住症状态，且达到最大强度；匹莫齐特的作用也是剂量依赖性的，尽管僵住症明显，但未达到最大强度。相比之下，硫利达嗪、氯氮平和舒必利各自引起的僵住症反应非常微弱，但很明确，尽管未显示出剂量依赖性。用α-甲基对酪氨酸预处理动物可显著增强氟哌啶醇、氟奋乃静、匹莫齐特、硫利达嗪和舒必利的僵住症作用，但未能改变氯氮平的作用。所有药物的阈下僵住症剂量与胆碱能药物RS86的阈下剂量在产生僵住症方面明显协同作用。同样，所有测试的“抗精神病”药物均显示以剂量依赖性方式降低苯丙胺、阿扑吗啡和诺米芬辛诱导的刻板行为强度，但只有氟哌啶醇、氟奋乃静和匹莫齐特能够实现100%抑制。氟哌啶醇、氟奋乃静和匹莫齐特的抗刻板行为能力对苯丙胺最为明显，但硫利达嗪、氯氮平和舒必利并非一直如此。典型和非典型抗精神病药物的阈剂量或甚至阈下剂量与RS86的阈剂量联合使用，在拮抗苯丙胺、阿扑吗啡和诺米芬辛的刻板行为作用方面明显协同。
