Drugs affecting acetylcholine receptors

Drugs acting at ganglion nicotinic receptors

As the same receptors are present at the ganglia of both the sympathetic and parasympathetic arms of the ANS, they cannot be differentiated pharmacologically.  Being ionotropic receptors, overstimulation can lead to depolarization blockade.  Thus, there is the potential for both agonists and antagonists to inhibit ganglionic neurotransmission.  Although ganglion blocking drugs have been used in the past in the treatment of hypertension, they are now considered clinically obsolete.

Drugs acting at muscarinic receptors

While subtypes of muscarinic receptors have been identified, the homogeneity of the orthosteric binding site at all subtypes means that there are few drugs which show selectivity for one subtype over others.

Muscarinic receptor agonists

 Agonists of muscarinic receptors mimic the actions of the parasympathetic nervous system.  These include:

• a decrease in heart rate and in atrial contraction
• indirect vasodilatation due to stimulation of NO from vascular endothelial cells
• contraction of smooth muscle of the gastrointestinal tract along with relaxation of the sphincters
• stimulation of exocrine glands leading to gastric acid secretion, salivation, lacrimation and sweating
• contraction of the detrusor muscle and relaxation of the bladder sphincters, leading to urination
• constriction of the pupil and the ciliary muscle of the eye, leading to miosis and decreased intraocular pressure

The effects of muscarinic agonists will depend on their duration of action (which can be determined by their susceptibility to breakdown by cholinesterases), their selectivity for muscarinic receptors over nicotinic receptors and their selectivity for the various muscarinic receptor subtypes.   For example, ACh is of no use as a therapeutic, due to its rapid breakdown and ability to stimulate all cholinoreceptor subtypes.  In contrast, bethanechol shows limited selectivity for M₃ receptors and is not susceptible to hydrolysis by cholinesterase.  It is used to in some situations to stimulate gastrointestinal motility or bladder emptying.   Muscarinic agonists are also used in opthalmology to cause pupil constriction and/or decrease intraocular pressure. 

Muscarinic receptor antagonists

Muscarinic receptor antagonists oppose the actions of the parasympathetic nervous system.  Examples of antagonists include atropine and hyoscine (scopolamine) which are found in the plants Atropa belladonna and Datura stramonium.  Ingestion of these antagonists can cause a range of peripheral (flushing, dry mouth, blurred vision, dilated pupils, tachycardia, urinary retention, constipation and hyperthermia) and central (confusion, hallucinations agitation, coma and convulsions) effects.  Synthetic and semi-synthetic antagonists have been developed and these differ in their pharmacokinetics (duration of action and distribution) and selectivity for the muscarinic receptor subtypes.  Therapeutic uses of muscarinic antagonists include:

• to cause pupil dilation to facilitate eye examinations (e.g. atropine; tropicamide)
• to cause relaxation of bronchial smooth muscle in COPD (e.g. ipratropium)
• to decrease gastric motility (e.g. hyoscine)
• to decrease bladder emptying (e.g. oxybutynin)

The involvement of muscarinic receptors in vomiting and emesis provides the rationale for the use of muscarinic antagonists to prevent motion sickness.