Ossowska K, Wolfarth S
Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Pol J Pharmacol. 1995 Mar-Apr;47(2):99-107.
Data concerning the incidence of extrapyramidal symptoms and the development of the supersensitivity to dopamine after administration of depot neuroleptics are controversial. The aim of the study was to examine the influence of depot neuroleptics on the sensitivity of dopamine receptors and GABA nigral receptors. Haloperidol decanoate (30 or 60 mg/kg im) and fluphenazine decanoate (12.5 or 25 mg/kg im) were injected twice at a 15 day interval. These treatments induced weak but very long-lasting catalepsy (60-105 days depending on the neuroleptic and its dose). The only significant enhancement of the apomorphine (0.25 mg/kg sc) stereotypy was observed 135 days after the lower dose of haloperidol and 230 days after the lower dose of fluphenazine. Haloperidol decanoate (30 mg/kg) did not influence the number of contralateral rotations induced by muscimol (10 or 25 ng/0.5 microliter) injected into the substantia nigra pars reticulata 35, 55 and 135 days after the first injection. Present results indicate that the dopaminergic supersensitivity after administration of depot neuroleptics is weak and appears very late, and that haloperidol decanoate does not induce nigral supersensitivity to GABA. It is suggested that the depot neuroleptics might induce less extrapyramidal symptoms in the clinic than the daily neuroleptic treatment.
关于长效抗精神病药物给药后锥体外系症状的发生率以及对多巴胺超敏反应的发展的数据存在争议。本研究的目的是检验长效抗精神病药物对多巴胺受体和黑质GABA受体敏感性的影响。癸酸氟哌啶醇(30或60毫克/千克,肌肉注射)和癸酸氟奋乃静(12.5或25毫克/千克,肌肉注射)每隔15天注射两次。这些治疗引发了轻微但持续时间很长的僵住症(60 - 105天,取决于抗精神病药物及其剂量)。仅在较低剂量的氟哌啶醇给药135天后以及较低剂量的氟奋乃静给药230天后,观察到阿扑吗啡(0.25毫克/千克,皮下注射)刻板行为有显著增强。在首次注射后35、55和135天,癸酸氟哌啶醇(30毫克/千克)对注射到黑质网状部的蝇蕈醇(10或25纳克/0.5微升)诱导的对侧旋转次数没有影响。目前的结果表明,长效抗精神病药物给药后的多巴胺能超敏反应较弱且出现得很晚,并且癸酸氟哌啶醇不会诱导黑质对GABA的超敏反应。有人提出,在临床上长效抗精神病药物可能比每日使用抗精神病药物治疗引发的锥体外系症状更少。