Cholinomimetics

1. By; Ömer ASLANKAN
Cholinomimetics (Direct acting)
Direct acting
cholinoceptor activating drugs so agonist
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Directly bind to cholinoceptor.
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Cholinoceptor; receptor of ACh and other cholinoceptor activating agents
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2 major subgroups: Directly activating acetylcholine receptors or inhibiting acetylcholinestherase
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Direct acting cholinomimetics act on nicotinic and muscarinic receptors
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Acetylcholine: prototype acts directly on M and N receptors
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Neostigmine: indirect-acting prototype, cholinesterase inhibitor
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Choline ester
Ester of acetic acid; Acetylcholine and methacholine
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Ester of carbamic acid; carbachol and bethanechol
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Alkaloids
Muscarine and nicotine
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Derivative; pilocarpine, lobeline, oxotremorine
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Cholinergic receptors
Are protein macromolecules having speci c sensitivity to acetylcholine.
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Have two groups; M and N cholinoceptors.
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Muscarinic receptor
are G protein coupled (GPCRs)
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E ector organ; heart, exocrine gland, presynaptic nerve
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Have 5 types receptors; M1, M3, M5 (stimulant receptors) and M2, M4 (inhibitory receptors)
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M1 M3 M5 are Gq coupled and cause increase in IP3, DAG cascade
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M2 M4 are Gi coupled and decrease cAMP synthesis
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Nicotinic receptor
Ion Channel linked receptor
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Autonomic ganglia ( sympathetic and parasympathetic)
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Neuromuscular junction;
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skeletal muscle, somatic nerve innervation
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Immediate depolarization of motor end plate
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Increase Sodium and potassium permeability
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Strong contraction of muscle
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CNS
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muscarinic Toxicity
diarrhea, salivation, sweating, cutaneous vasodilation, bronchoconstriction
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Inhibited by Atropine
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nicotinic Toxicity
Central stimulant action … convulsion, coma, respiratory depression
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Skeletal muscle end plate depolarization … muscle weakness, respiratory paralysis (Not response to
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AChE inhibitor)
Hypertension, cardiac arrhythmia
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Symptomatic treatment … Atropine, Anti- convulsant
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Long term e ect of nicotine from cigarette smoke
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Vascular disease
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2. Varenicline – Partial N agonist; used to assist smoking cessation
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Bethanechol – M agonist; nonobstructive GI dysmotility (post-op ileus, neurogenic ileus),
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nonobstructive urinary retention (post-op, post-partum, neurogenic bladder)
Pilocarpine – M agonist; Dry mouth (Sjögren’s syndrome, radiation damage), glaucoma (ciliary
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muscle contraction, pupil constriction)
Carbachol – M and N agonist; glaucoma (pupillary constriction)
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Methacholine – M agonist; Mimics parasympathetic e ects, such as bronchoconstriction. Can
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exacerbate asthma or COPD, and used in diagnostics (methacholine challenge test).