Muscarinic agonist
Muscarinic acetylcholine receptor agonist
- Exocrine secretion (saliva, tears, sweat, gastric acid)
- Smooth-muscle contraction (bladder, gut, bronchi); nausea
- Miosis, ↓ intraocular pressure (ophthalmic)
- Bradycardia (M2)
- Bronchospasm (M3)
- Antipsychotic (M4) and procognitive (M1) if BBB-crossing
Muscarinic agonist (1/4)
- Presynaptic autoreceptor → inhibits ACh release
- Undesirable effects:
- ➔ bradycardia
- ➔ AV block
- ➔ acetylcholinesterase (AChE) inhibitors ◇ listed below
- Exocrine gland stimulation
- ➔ saliva, tears, gastric acid, pancreatic enzymes, mucus
Muscarinic agonist (2/4)
- Smooth muscle contraction
- ➔ ↑ GI motility → cramping, diarrhea
- ➔ bronchoconstriction
- Pupillary constriction (miosis)
- Ciliary muscle contraction (accommodation for near vision)
- Pancreatic β-cell M3 activation → ↑ insulin secretion
- Enhances cognition
Muscarinic agonist (3/4)
- May improve negative symptoms of schizophrenia
- Increases neuronal excitability
- ➔ enhances glutamatergic transmission
- ➔ ↓ seizure threshold
- Gastric acid secretion
- Salivation
- ➔ may contribute to clozapine-induced hypersalivation
- Modulates cholinergic activation of dopamine firing in the Ventral Tegmental Area (VTA), a midbrain hub of reward and motivation
- ➔ M5 is the predominant muscarinic subtype expressed on midbrain dopaminergic neurons
Muscarinic agonist (4/4)
- Cerebral vasodilation (endothelial)
- M4 activation may reduce striatal DA release
- ➔ suggested for clozapine (Morrison et al, 2025), but disputed (Reynolds, 2025) ◇ not a proven mechanism of clozapine
Drugs with this mechanism (8)
- Aceclidine — Muscarinic agonist used topically for glaucoma and presbyopia.
- Acetylcholine — Endogenous neurotransmitter at muscarinic and nicotinic receptors.
- Bethanechol — Muscarinic agonist for non-obstructive urinary retention.
- Carbachol — Nonselective cholinergic agonist used in ophthalmology.
- Cevimeline — Muscarinic agonist for dry mouth in Sjogren syndrome.
- Norclozapine — Active clozapine metabolite; M1 agonist implicated in some clozapine effects.
- Pilocarpine — Muscarinic agonist for glaucoma and dry mouth.
- Xanomeline — M1/M4 muscarinic agonist; the antipsychotic partner in Cobenfy.
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