Tropane Alkaloids, Muscarinic Antagonism, and NMDAR Modulation in Datura Neurotoxicity

Datura species from family Solanaceae, containing both Datura stramonium and Datura metel, show a complex pharmacological duality as being a historically important therapeutic as well as a potent neurotoxin. This paper reviews the neurobiological mechanisms through which Datura disrupt central and peripheral nervous system function. Datura has primary tropane alkaloids including hyoscyamine, scopolamine, and atropine, that induce the classical anticholinergic toxidrome stems from competitive antagonism across metabotropic muscarinic acetylcholine receptor subtypes. Central blockade disrupts cognitive function, precipitating acute cognitive impairments, anterograde amnesia, delirium, and visual hallucinations, while peripheral inhibition induces severe tachycardia, anhidrosis, mydriasis, and hyperthermia. Regardless of acute neurotoxicity, purified tropane constituents maintain essential clinical roles in anesthesia, respiratory disorders, and movement conditions. Finally, we highlight emerging research frontiers, including pharmacogenomic profiling of Cytochrome P450 metabolism and advanced functional neuroimaging of effective connectivity under cholinergic disruption.