Alkaloids With Cholinergic Effects

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Nicotine (see also p. 173) is a social drug that lends its medicinal use as an adjunct to stopping its own abuse as tobacco. It is available as either gum to chew, as dermal patches or as an inhalation. These deliver a lower dose of nicotine than cigarettes and appear to be safe in patients with ischaemic heart disease. The patches are slightly better tolerated than the gum, which releases nicotine in a more variable fashion depending on the rate at which it is chewed and the salivary pH, which is influenced by drinking coffee and carbonated drinks. Nicotine treatment is reported to be nearly twice as effective as placebo in achieving sustained withdrawal from smoking (18% vs. 11% in one review).3 Treatment is much more likely to be successful if it is used as an aid to, not a substitute for, continued counselling. Bupropion is possibly more effective than the nicotine patch4 (see also p. 177).

Pilocarpine, from a South American plant (Pilocarpus spp.), acts directly on end-organs innervated by postganglionic nerves (parasympathetic system plus sweat glands); it also stimulates and then depresses the central nervous system. The chief clinical use of pilocarpine is to lower intraocular pressure in chronic simple glaucoma, as an adjunct to a topical beta-blocker; it produces miosis, opens drainage channels in the trabecular network and improves the outflow of aqueous humour. Oral pilocarpine is available for the treatment of xerostomia (dry mouth) in Sjogren's syndrome, or following irradiation of head and neck tumours. The commonest adverse effect is sweating; adverse cardiac effects have not been reported.

Arecoline is an alkaloid in the betel nut, which is chewed extensively throughout India and southeast Asia. Presumably the lime mix in the 'chews' provides the necessary alkaline pH to maximise its buccal absorption. It produces a mild euphoric effect like many cholinomimetic alkaloids.

3 Drug and Therapeutics Bulletin 1999; 37 (July issue).

4 Jorenby D E et al 1999 New England Journal of Medicine 340: 685-692.

Muscarine is of no therapeutic use but it has pharmacological interest. It is present in small amounts in the fungus Amanita muscaria (Fly agaric), named after its capacity to kill the domestic fly (Musca domestica); muscarine was so named because it was thought to be the insecticidal principle, but it is relatively nontoxic to flies (orally administered). The fungus may contain other anti-muscarinic substances and GABA-receptor agonists (such as muscimol) in amounts sufficient to be psychoactive in man.

Poisoning with these fungi may present with antimuscarinic, with cholinergic or with GABAergic effects. All have CNS actions. Happily, poisoning by Amanita muscaria is seldom serious. Species of Inocybe contain substantially larger amounts of muscarine (see Ch. 9). The lengths to which man is prepared to go in taking 'chemical vacations' when life is hard, are shown by the inhabitants of Eastern Siberia who used Amanita muscaria recreationally, for its cerebral stimulant effects. They were apparently prepared to put up with the autonomic actions to escape briefly from reality. The fungus was scarce in winter and the frugal devotees discovered that by drinking their own urine they could prolong the intoxication. Sometimes, in generous mood, the intoxicated person would offer his urine to others as a treat.

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