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β-咔啉生物碱在神经精神疾病方面的神经药理学潜力。

Neuropharmacological potentials of β-carboline alkaloids for neuropsychiatric disorders.

机构信息

Centre for Drug Research, Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia; Department of Chemical, Geological and Physical Sciences, Kwara State University, P. M. B., 1530, Malete, Ilorin, Nigeria.

Centre for Drug Research, Universiti Sains Malaysia, USM, 11800, Pulau Pinang, Malaysia.

出版信息

Eur J Pharmacol. 2021 Feb 15;893:173837. doi: 10.1016/j.ejphar.2020.173837. Epub 2020 Dec 25.

Abstract

Neuropsychiatric disorders are diseases of the central nervous system (CNS) which are characterised by complex pathomechanisms that including homeostatic failure, malfunction, atrophy, pathology remodelling and reactivity anomaly of the neuronal system where treatment options remain challenging. β-Carboline (βC) alkaloids are scaffolds of structurally diverse tricyclic pyrido[3,4-b]indole alkaloid with vast occurrence in nature. Their unique structural features which favour interactions with enzymes and protein receptor targets account for their potent neuropharmacological properties. However, our current understanding of their biological mechanisms for these beneficial effects, especially for neuropsychiatric disorders is sparse. Therefore, we present a comprehensive review of the scientific progress in the last two decades on the prospective pharmacology and physiology of the βC alkaloids in the treatment of some neuropsychiatric conditions such as depression, anxiety, Alzheimer's disease, Parkinson's disease, brain tumour, essential tremor, epilepsy and seizure, licking behaviour, dystonia, agnosia, spasm, positive ingestive response as demonstrated in non-clinical models. The current evidence supports that βC alkaloids offer potential therapeutic agents against most of these disorders and amenable for further drug design.

摘要

神经精神疾病是中枢神经系统(CNS)的疾病,其特征是复杂的发病机制,包括神经元系统的内稳态衰竭、功能障碍、萎缩、病理重塑和反应异常,而治疗选择仍然具有挑战性。β-咔啉(βC)生物碱是结构多样的三环吡啶[3,4-b]吲哚生物碱的骨架,在自然界中广泛存在。它们独特的结构特征有利于与酶和蛋白受体靶标相互作用,这解释了它们强大的神经药理学特性。然而,我们目前对它们在治疗某些神经精神疾病(如抑郁症、焦虑症、阿尔茨海默病、帕金森病、脑肿瘤、特发性震颤、癫痫和惊厥、舔行为、肌张力障碍、认知障碍、痉挛、阳性摄食反应)方面的这些有益作用的生物学机制的理解还很匮乏。因此,我们对过去二十年中βC 生物碱在治疗某些神经精神疾病方面的药理学和生理学的科学进展进行了全面综述,这些疾病包括抑郁症、焦虑症、阿尔茨海默病、帕金森病、脑肿瘤、特发性震颤、癫痫和惊厥、舔行为、肌张力障碍、认知障碍、痉挛、阳性摄食反应等。目前的证据支持βC 生物碱是大多数这些疾病的潜在治疗药物,并且适合进一步的药物设计。

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