## 3 Biosynthesis and Health Implications of Tropane Alkaloids
### Effect on Humans and Mechanism of Action  
Tropane alkaloids, along with other alkaloids, serve as a powerful defense mechanism for plants, reducing herbivore attack and inhibiting the growth of competing vegetation. However, these showed activity also against vertebrate animals representing a worrying source of contamination for food and feed [32; 33]. Human and animal exposure to TAs is primarily associated with the dietary consumption of some plants of the Solanaceae family such as _S. tuberosum_ L. (potato), _S. Iycopersicum_ L. (tomato), _S. melongena_ L. (eggplant), and _Capsicum autumn_ L. (epper). Seeds, leaves, roots, fruits, and flowers are frequently responsible for cross- contamination during harvest, and their toxicity ranges from mildly irritating to fatal [34]. TAs have a long history of intentional consumption by humans. In a recent work, the use of hallucinogenic drugs was evidenced during the bronze age about 3600 years ago [35]. Atropine and scopolamine were mostly detected via the analysis of human hairs from a burial site in Spain. This indicated the capability of these molecules to cross the blood-brain barrier to affect the central nervous system [36]. It is likely that these have been used to induce delirium, hallucinations, and altered sensory perception as part of ritualistic ceremonies by shamans. Their use as psychoactive drugs has been described also during the Medieval age [37]. For example, _Datura stramonium_, _Mandragora officinarum_, _Hyoscyamus niger_, and _Atropa belladonna_ have been used as sedatives, sleep inducing agents (henbane), aphrodisiacs, and panaceas (mandrake). Besides the pharmacological activities as narcotic analgesics or hallucinogens, TAs are considered model drugs for their anti-cholinergic effects [28]. For example, atropine, hyoscyamine, and scopolamine are primarily antagonists of the muscarinic acetylcholine (Ach) receptors and can induce several side effects based on the amount ingested [38]. Ach, acting as a neurotransmitter in many parts of the body, is most commonly associated with the neuromuscular junction. Typically,  
Figure 2: Biosynthetic pathway for tropane alkaloids formation. Enzyme symbols: ODC = ornitine decarboxylase; PMT = putrescine _N_-methyltransferase; MPO = _N_-methylputrescine oxidase; * = spontaneous cyclization; PKS = pyrrolidine ketide synthase; CYP82M3 = tropinone synthase; TRI = tropinine reductase I; TRII = tropinone reductase II; LS = littorine synthase; CYP80F1 = littorine mutase; H6H = hyoscyamine 6\(\beta\)-hydroxylase; ArAT4 = aromatic amino acid aminotransferase; PPAR = phenylpyruvic acid reductase; UGT1 = phenyllactate UDP-glycostransferase. acetylcholine is an excitatory mediator involved in numerous physiological functions, such as regulating cardiac contractions and blood pressure, intestinal peristalsis, and glandular secretion. Hence, the downstream effects of TAs have been well known since the beginning of the previous century. Inhibition of the acetylcholine receptors of the parasympathetic nervous system determines constriction of the pupil, vasodilation, and moderation of the heartbeat [39]. This is the reason TAs have been and still are widely used drugs for the treatment of motion sickness, ophthalmic surgery, and for bradycardia treatment [40; 41]. TAs, for their parasympatholytic mode of action, are classified as essential medicines by the World Health Organization for the treatment of organophosphate, pesticide poisoning, motion sickness, gastrointestinal spasms, cardiac arrhythmia, Parkinson's disease, anesthesia, analgesia, cough, and asthma relief [42; 43]. A dose of 10 mg or above of atropine and scopolamine is able to produce direct toxicity [38; 44]. Clinical symptoms of their toxicity are change in heart rate, decreased production of salivary secretions, bronchial and sweat glands, pupil dilation, paralysis of accommodation of the eye, inhibition of micturition, reduction in gastrointestinal tone, inhibition of gastric acid secretion, hallucinations, and death [45].