Beauty of the beast: anticholinergic tropane alkaloids in therapeutics

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.