Mierzejewski Pawel, Kolaczkowski Marcin, Marcinkowska Monika, Wesolowska Anna, Samochowiec Jerzy, Pawlowski Maciej, Bienkowski Przemyslaw
Department of Pharmacology, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957 Warsaw, Poland.
Faculty of Pharmacy, Collegium Medicum, Jagiellonian University, 9 Medyczna St., 30-688 Krakow, Poland; Adamed Ltd., Pienkow 149, 05-152 Czosnow, Poland.
Eur J Pharmacol. 2016 Feb 15;773:51-8. doi: 10.1016/j.ejphar.2016.01.009. Epub 2016 Jan 26.
Aside from their use in the treatment of anxiety disorders and insomnia, benzodiazepines and other GABAA receptor positive modulators are widely used as add-on treatments in schizophrenic and non-schizophrenic psychoses. However, there is relatively little direct clinical or pre-clinical evidence for antipsychotic effects of GABAergic medications. Previous studies have indicated that zolpidem, a GABAergic drug acting preferentially at α1-containing GABAA receptors, may produce catalepsy through interactions with dopaminergic neurotransmission. The aim of the present study was to investigate effects of zolpidem in experimental models of antipsychotic activity and extrapyramidal side effects in Wistar rats. Effects of zolpidem were compared with that of a classic benzodiazepine drug, diazepam and a second-generation antipsychotic medication, risperidone. High doses of risperidone (10.0mg/kg, i.p.) and zolpidem (10.0mg/kg, i.p.), but not diazepam, induced relatively short-lasting cataleptic responses in the bar test. Zolpidem and risperidone, but not diazepam, produced some antipsychotic-like effects at doses, which produced no catalepsy and did not inhibit spontaneous locomotor activity and apomorphine-induced stereotypies. The present results tend to indicate that zolpidem exerts some neuroleptic-like effects at doses, which do not produce motor side effects. Our findings may provide further rationale for the development of new subtype-selective GABAA receptor modulators for the treatment of psychotic symptoms.
除了用于治疗焦虑症和失眠外，苯二氮䓬类药物和其他GABAA受体正向调节剂还被广泛用作精神分裂症和非精神分裂症性精神病的辅助治疗药物。然而，关于GABA能药物抗精神病作用的直接临床或临床前证据相对较少。先前的研究表明，唑吡坦是一种优先作用于含α1的GABAA受体的GABA能药物，可能通过与多巴胺能神经传递相互作用而产生僵住症。本研究的目的是研究唑吡坦在Wistar大鼠抗精神病活性和锥体外系副作用实验模型中的作用。将唑吡坦的作用与经典苯二氮䓬类药物地西泮和第二代抗精神病药物利培酮进行比较。高剂量的利培酮（10.0mg/kg，腹腔注射）和唑吡坦（10.0mg/kg，腹腔注射），而不是地西泮，在棒试验中诱导出相对短暂的僵住反应。唑吡坦和利培酮在不产生僵住症、不抑制自发运动活性和阿扑吗啡诱导的刻板行为的剂量下产生了一些抗精神病样作用。目前的结果倾向于表明，唑吡坦在不产生运动副作用的剂量下发挥了一些抗精神病样作用。我们的发现可能为开发用于治疗精神病症状的新型亚型选择性GABAA受体调节剂提供进一步的理论依据。
