Cholinergic blocking drugs are a group of drugs that block the action of acetylcholine (ACh), a neurotransmitter, in synapses of the cholinergic nervous system. They block acetylcholine from binding to cholinergic receptors, namely the nicotinic and muscarinic receptors.
These agents have broad effects due to their actions in nerves located vastly over the body. These nerves include motor nerves in somatic nervous system which innervate skeletal muscles as well as nerves in the sympathetic and parasympathetic nervous systems. Organs that receive innervations from these systems include exocrine glands, heart, eyes, gastrointestinal tract etc. Antimuscarinic and antinicotinic agents can increase heart rate, inhibit secretions, and gastrointestinal motility.
Naturally occurring antimuscarinics were found in alkaloids from Belladonna (Solanaceae) plants. They were used as deadly poison and pupil-dilating cosmetics. While curare, the naturally occurring antinicotinics derived from Chondrodendron and Strychnos, was a poison used by South American Indians for hunting.
According to their site of actions, cholinergic blocking drugs can be classified into two general types — antimuscarinic and antinicotinic agents. Antimuscarinic agents (also known as muscarinic antagonists), including atropine and hyoscine, block acetylcholine at the muscarinic acetylcholine receptors. Antinicotinic agents (also known as ganglionic blockers, neuromuscular blockers), including tubocurarine and hexamethonium, block acetylcholine action at nicotinic acetylcholine receptors. Their effects are based on the expression of corresponding receptors in different parts of the body.
There are many adverse effects, interactions and contraindications for antinicotinic and antimuscarinic agents. Adverse effects include hypotension, dry mouth, dry eyes etc. They interact with grapefruit juice and various medications, e.g. warfarin, metoclopramide. Therefore, cautions should be exercised and advice from medical professionals should be sought before using medications.
History
Discovery of cholinergic nervous system
In 1900, Reid Hunt, a pharmacologist (1870-1948), realised a fall in blood pressure in rabbits after removing adrenaline (epinephrine) from adrenal glands extract. While he initially attributed this effect to choline, he later discovered acetylcholine was 100 000 times more potent in lowering blood pressure.
British physiologist Sir Henry Hallett Dale (1875-1968) observed acetylcholine for causing blood vessel dilation and slowing down heart rate. In 1914, Dale noted that the physiological effect of acetylcholine resembled the stimulation of parasympathetic nervous system and hypothesized acetylcholine as the neurotransmitter. Later, Dale named substances that mimic acetylcholine action as “cholinergics”.
In 1914, Dale also distinguished two types of activities of acetylcholine, namely muscarinic and nicotinic, as they mimic the effects of injecting muscarine, extracted from poisonous mushroom Amanita muscaria, and nicotine.
Antimuscarinic agents
Naturally occurring antimuscarinics were found in alkaloids from Belladonna (Solanaceae) plants. They were used as deadly poison in Roman Empire and Middle Ages. The name Belladonna, meaning beautiful ladies, was derived from women using berry juice from the plant cosmetically to dilate their pupils.
The mydriatic effect was studied by the German chemist Friedlieb Ferdinand Runge (1795-1867), in which the active ingredient, atropine, was first discovered by Vaquelin in 1809 and was first isolated by Heinrich F. G. Mein in 1813.
In the 1850s, atropine was used as antispasmodic in asthma treatment and as morphine antidote for its mydriatic effect. Bezold and Bloebaum showed that atropine blocked the effects of vagal stimulation on the heart in 1867. Subsequently in 1872, Heidenhain found its ability to prevent salivary secretion.
Antinicotinic agents
Curare, derived from Chondrodendron and Strychnos, was used as poison by South American Indians to coat arrow tips or blow-pipe darts for hunting animals. It is first identified when Spanish soldiers were attacked by these indigenous tribes in the 16th century.
In 1906, Langley studied the actions of nicotine and curare on chicken and frog muscles. Curare was found to block the stimulant action of nicotine in both innervated and chronically denervated muscles. In 1940, Jenkinson identified tubocurarine as a competitive antagonist of acetylcholine.