Ahmadu Peter Uchogu, Victor Ejigah, Ameh Fidelis Solomon
Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development, Federal Ministry of Health, P.M.B 21, Garki, Abuja, Nigeria.
Department of Pharmaceutics, College of Pharmacy, Howard University, Washington, DC, USA.
IBRO Neurosci Rep. 2021 Dec 3;12:12-19. doi: 10.1016/j.ibneur.2021.11.002. eCollection 2022 Jun.
Nevirapine (NVP) is non-nucleoside reverse transcriptase inhibitor and an anti-retroviral drug (ARV) with the highest BBB penetrating ability. Its specific pharmacologic effects on central nervous system (CNS) are not well known. The objective of the study was to investigate some CNS effects of Nevirapine. Oral acute toxicity test (Lorke, 1983) was used to estimate the LD. Exploratory or sedative effects were tested using open field test(OFT), Hole-board test (HBT), diazepam-induced sleeping time test, and ketamine-induced sleeping time test. Five groups of mice were used (5 mice /group). The negative control group received vehicle (distilled water) (10 mL /kg) while groups II, III, and IV received NVP- 15.625 mg/kg, 31.25 mg/kg, 62.5 mg/kg body weight respectively while group V received 0.25 mg/kg of diazepam intraperitoneal. Groups I to IV were treated orally. The oral LD was determined to be 2154. 07 mg/kg. NVP, in a dose dependent fashion, increased the number of line-crossing in the OFT. Also, NVP in a dose-dependent fashion, significantly reduced the duration of diazepam-induced sleeping time as well as delayed onset. NVP significantly potentiated ketamine-induced sleeping time duration. Nevirapine possess excitatory effects possibly through antagonism of GABA receptors. Nevirapine causes wakefulness (shortening of sleep) possibly via antagonism of GABAergic neurotransmission.
奈韦拉平(NVP)是一种非核苷类逆转录酶抑制剂,也是一种血脑屏障穿透能力最强的抗逆转录病毒药物(ARV)。其对中枢神经系统(CNS)的具体药理作用尚不清楚。本研究的目的是调查奈韦拉平对中枢神经系统的一些影响。采用口服急性毒性试验(Lorke,1983)来估计半数致死量(LD)。使用旷场试验(OFT)、洞板试验(HBT)、地西泮诱导睡眠时间试验和氯胺酮诱导睡眠时间试验来测试探索性或镇静作用。使用了五组小鼠(每组5只小鼠)。阴性对照组接受赋形剂(蒸馏水)(10 mL/kg),而第二、三、四组分别接受15.625 mg/kg、31.25 mg/kg、62.5 mg/kg体重的奈韦拉平,第五组腹腔注射0.25 mg/kg的地西泮。第一至四组经口给药。口服半数致死量测定为2154.07 mg/kg。奈韦拉平以剂量依赖性方式增加了旷场试验中的穿越次数。此外,奈韦拉平以剂量依赖性方式显著缩短了地西泮诱导的睡眠时间并延迟了起效时间。奈韦拉平显著延长了氯胺酮诱导的睡眠时间。奈韦拉平可能通过拮抗GABA受体而具有兴奋作用。奈韦拉平可能通过拮抗GABA能神经传递而导致清醒(睡眠缩短)。