Cholinomimetic Alkaloids

CHOLINOMIMETIC ALKALOIDS

Pilocarpine It is obtained from the leaves of Pilocarpus microphyllus and other species. It has prominent muscarinic actions and also stimulates ganglia—mainly through ganglionic muscarinic receptors.

Pilocarpine causes marked sweating, salivation and increases other secretions as well. The cardiovascular effects are complex. Small doses generally cause fall in BP (muscarinic), but higher doses elicit rise in BP and tachycardia which is probably due to ganglionic stimulation (through ganglionic muscarinic receptors). Applied to the eye, it penetrates cornea and promptly causes miosis, ciliary muscle contraction and fall in intraocular tension lasting 4–8 hours.

Pilocarpine is used only in the eye as 0.5–4% drops. It is a third line drug in open angle glaucoma. An initial stinging sensation in the eye and painful spasm of accommodation are frequent side effects. Other uses as a miotic are— to counteract mydriatics after they have been used for testing refraction and to prevent/break adhesions of iris with lens or cornea by alternating it with mydriatics.

PILOCAR 1%, 2%, 4% eye drops, CARPINE 0.5% eyedrops, PILODROPS 2% eyedrops.

Muscarine It occurs in poisonous mushrooms Amanita muscaria and Inocybe species and has only muscarinic actions. It is not used therapeutically but is of toxicological importance.

Mushroom poisoning Depending on the toxic principle present in the particular species, at least 3 types of mushroom poisoning is known.

Muscarine type (Early mushroom poisoning) due to Inocybe and related species. Symptoms characteristic of muscarinic actions appear within an hour of eating the mushroom, and are promptly reversed by atropine.

Hallucinogenic type It is due to muscimol and other isoxazole compounds which are present in A. muscaria and related mushrooms in much larger quantities than is muscarine. These compounds activate amino acid receptors, and block muscarinic receptors in the brain; have hallucinogenic property. Manifestations of poisoning are primarily central. There is no specific treatment and atropine is contraindicated. Another hallucinogenic mushroom is Psilocybe mexicana whose active principle psilocybine is a tryptaminergic (5HT related) compound.

Phalloidin type (Late mushroom poisoning) It is due to peptide toxins found in A. phalloides, Galerina and related species. These inhibit RNA and protein synthesis. The symptoms start after many hours and are due to damage to the gastrointestinal mucosa, liver and kidney. Treatment consists of supportive measures. Thioctic acid may have some antidotal effect.

Arecoline It is found in betel nut Areca catechu and has muscarinic as well as nicotinic actions, including those on skeletal muscle endplate. It also has prominent CNS effect: has been tried in dementia as an enhancer of cognitive functions, but not found useful—has no therapeutic use.