Shim Kyu Hwan, Kang Min Ju, Sharma Niti, An Seong Soo A
Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-Gu, Seongnam, 461-701, South Korea.
Department of Neurology, Veterans Health Service Medical Center, Veterans Medical Research Institute, Seoul, South Korea.
Nat Prod Bioprospect. 2022 Sep 16;12(1):33. doi: 10.1007/s13659-022-00357-w.
Tropane alkaloids (TAs) are among the most valued chemical compounds known since pre-historic times. Poisonous plants from Solanaceae family (Hyoscyamus niger, Datura, Atropa belladonna, Scopolia lurida, Mandragora officinarum, Duboisia) and Erythroxylaceae (Erythroxylum coca) are rich sources of tropane alkaloids. These compounds possess the anticholinergic properties as they could block the neurotransmitter acetylcholine action in the central and peripheral nervous system by binding at either muscarinic and/or nicotinic receptors. Hence, they are of great clinical importance and are used as antiemetics, anesthetics, antispasmodics, bronchodilator and mydriatics. They also serve as the lead compounds to generate more effective drugs. Due to the important pharmacological action they are listed in the WHO list of essential medicines and are available in market with FDA approval. However, being anticholinergic in action, TA medication are under the suspicion of causing dementia and cognitive decline like other medications with anticholinergic action, interestingly which is incorrect. There are published reviews on chemistry, biosynthesis, pharmacology, safety concerns, biotechnological aspects of TAs but the detailed information on anticholinergic mechanism of action, clinical pharmacology, FDA approval and anticholinergic burden is lacking. Hence the present review tries to fill this lacuna by critically summarizing and discussing the above mentioned aspects.
托烷生物碱(TAs)是自史前时代以来已知的最有价值的化合物之一。茄科(黑莨菪、曼陀罗、颠茄、藏东莨菪、药用曼陀罗、澳茄属)和古柯科(古柯)的有毒植物是托烷生物碱的丰富来源。这些化合物具有抗胆碱能特性,因为它们可以通过与毒蕈碱和/或烟碱受体结合来阻断中枢和外周神经系统中神经递质乙酰胆碱的作用。因此,它们具有重要的临床意义,被用作止吐药、麻醉剂、解痉药、支气管扩张剂和散瞳剂。它们还作为先导化合物用于开发更有效的药物。由于其重要的药理作用,它们被列入世界卫生组织基本药物清单,并已获得美国食品药品监督管理局(FDA)批准在市场上销售。然而,由于具有抗胆碱能作用,托烷生物碱药物像其他具有抗胆碱能作用的药物一样,受到导致痴呆和认知能力下降的怀疑,有趣的是,这种怀疑是不正确的。关于托烷生物碱的化学、生物合成、药理学、安全问题、生物技术方面已有发表的综述,但缺乏关于其抗胆碱能作用机制、临床药理学、FDA批准情况和抗胆碱能负担的详细信息。因此,本综述试图通过批判性地总结和讨论上述方面来填补这一空白。