Mechanism of Action and Organ System Effects
These drugs block tissue muscarinic receptors, abolishing the effects of the parasympathetic nervous system. This produces effects that directly oppose parasympathetic activation:
- Visual system: Relaxation of the sphincter pupillae muscle leads to pupil dilation (mydriasis). Simultaneous relaxation of the ciliary muscle causes tension on the suspensory ligaments (zonules of Zinn), flattening of the lens, and adjustment of the eye for distance vision (inducing cycloplegia). Combined, these effects impair aqueous humor outflow, potentially precipitating an increase in intraocular pressure (making these drugs strictly contraindicated in glaucoma).
- Respiratory system: Decreases smooth muscle tone (producing bronchodilation) and reduces bronchial gland secretion.
- Gastrointestinal and urinary tracts: Suppresses motility and decreases smooth muscle tone in the intestines and urinary bladder. Digestive secretions are significantly reduced.
- Sweat glands: A special case. They receive sympathetic innervation, but signal transmission at the effector junction is mediated by acetylcholine. By blocking these receptors, the drugs reduce sweating and cause dry skin.
Plant Sources and Chemical Structure
Historically, this group is represented by tropane alkaloids extracted from the Nightshade family (Solanaceae): deadly nightshade (Atropa belladonna), henbane, jimsonweed, and scopolia.
Our classic representative is atropine. In the living plant, it exists as L-hyoscyamine, but during chemical extraction it transforms into a racemic mixture of isomers. This lipophilic, nonpolar compound readily crosses tissue barriers.
Other plant alkaloids include scopolamine (an ester of scopine and tropic acid) and platyphylline (an alkaloid from Senecio platyphyllus, a methylpyrrolizidine derivative).
Clinical Applications
Muscarinic antagonists are widely used in gastroenterology, urology, and surgery:
- Peptic ulcer disease: These drugs reduce hydrochloric acid secretion. Atropine acts non-selectively, whereas the more modern pirenzepine selectively blocks only M1 receptors, providing a superior safety profile.
- Spastic conditions: Thanks to their potent antispasmodic effect, these agents are effective in intestinal and biliary colic (their effect is weaker in renal colic).
- Acute pancreatitis: Atropine inhibits trypsinogen secretion, preventing its premature activation and protecting the pancreas from autodigestion.
- Urology (overactive bladder): tolterodine and oxybutynin relax the detrusor muscle of the bladder. Newer agents include the non-selective trospium chloride and drugs with high affinity for M3 receptors — darifenacin and solifenacin.
Related Group: Ganglionic Blockers
The classification of agents blocking cholinergic synapses also includes ganglionic blockers (which block N-receptors in autonomic ganglia). They are divided into two subgroups:
- Hydrophilic (polar) agents: Bisquaternary amines (hexamethonium, pentamin) and sulfonium compounds (trimethaphan). They do not cross the blood-brain barrier. Intermediate-acting drugs are used to manage hypertensive crises, while short-acting agents are used for controlled hypotension during surgical procedures.
- Lipophilic (nonpolar) agents: Secondary amine mecamylamine. It easily penetrates the central nervous system. It is used in the treatment of nicotine dependence because it displaces nicotine from receptors and eliminates feelings of euphoria.