Kumari Namrata, Agrawal Saurabh, Luthra Pratibha Mehta
Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India.
Dr. B.R. Ambedkar Center for Biomedical Research (ACBR), University of Delhi, Delhi, India.
Neurosci Lett. 2017 Apr 24;647:53-60. doi: 10.1016/j.neulet.2017.03.033. Epub 2017 Mar 20.
A receptor antagonists emerged as potential candidate for management of Parkinson's disease. Earlier we had reported the therapeutic potential of 1-(7-imino-3-propyl-2,3-dihydrothiazolo[4,5-d]pyrimidin-6(7H)-yl) urea (IDPU) as A receptor antagonist. Herein, we have investigated the effect of IDPU in attenuation of haloperidol induced Parkinson like symptoms in rats. It has successfully restored hypo-locomotion induced by haloperidol and NECA. IDPU also displayed protective effect against oxidative stress induced by chronic haloperidol treatment in rats. The antidepressant activity of IDPU was determined in mice showed that it imperatively reduced depression like symptoms in well-established depression models viz. TST and FST. Additionally, IDPU was found to be a safe and non-toxic chemical entity in acute, sub-acute and neurotoxicity studies. In silico study of IDPU showed acceptable physicochemical parameters and in vitro screening exhibited satisfactory metabolic stability. This study clearly indicates that A receptor antagonist IDPU is able to ameliorate Parkinsonian symptoms without exerting any significant toxicity.
一种受体拮抗剂成为帕金森病治疗的潜在候选药物。此前我们曾报道1-(7-亚氨基-3-丙基-2,3-二氢噻唑并[4,5-d]嘧啶-6(7H)-基)脲（IDPU）作为一种受体拮抗剂的治疗潜力。在此，我们研究了IDPU对减轻大鼠氟哌啶醇诱导的帕金森样症状的作用。它成功恢复了氟哌啶醇和NECA诱导的运动减少。IDPU还对慢性氟哌啶醇治疗诱导的大鼠氧化应激显示出保护作用。在小鼠中测定的IDPU的抗抑郁活性表明，它在成熟的抑郁模型即悬尾试验（TST）和强迫游泳试验（FST）中显著减轻了抑郁样症状。此外，在急性、亚急性和神经毒性研究中，IDPU被发现是一种安全无毒的化学实体。对IDPU的计算机模拟研究显示出可接受的物理化学参数，体外筛选显示出令人满意的代谢稳定性。这项研究清楚地表明，受体拮抗剂IDPU能够改善帕金森症状而不产生任何明显毒性。
