Skeletal NMJ pharmacology

Nicotine

Nicotinic agonist

Nicotinic receptor -> activate

acts through the nicotinic receptors in the brain

Succinylcholine

Depolarizing blocker; agonist

Nicotinic -> activate via depolarizing

ACh Analog; rapid onset; initial fasciculation

phase 1; repolarization phase 2 block. Dantrolene

D- Tubocurarine

Non-depolarizing NMJ blocker; antagonist

competitive nicotinic antagonist

Classic Skeletal NMJ blocker, prevents ACh-mediated

depolarizations

Pancuronium

Non-depolarizing NMJ blocker; antagonist

competitive nicotinic antagonist

long acting; causes paralysis Without depolarization;

tachycardia possible. Increased potency w/anesthetics

vecuronium;

Rocuronium;

Atracurium

Non-depolarizing NMJ blocker; antagonist

competitive nicotinic antagonist

Not long lasting; no tachycardia;

↑ potency w/ anesthetics

Edrophonium

Non-Covalent AChE inhibitor

Inhibits acetylcholinesterase

Highly charged; does NOT cross BBB; short-

acting

Tacrine; Donepezil

Non-Covalent AChE inhibitor

Inhibits acetylcholinesterase

Binds choline (anionic) binding site and prevents

ACh binding to cholinesterase

physostigmine; Neostigmine; Pyridostigmine

Reversible Covalent AChE inhibitor

Reversible Covalent bond to AChE

Sustained but reversible AChE inhibition;

enzyme eventually reactivates; Increased ACh

treatment for myasthenia gravis

carbaryl

Carbamate AChE inhibitor

Reversible covalent bond to AChE

Garden Insecticide

Malathion; Parathion

organophosphate AChE inhibitor

Irreversible AChE inhibition

very stable intermediate formed

Sarin

organophosphate AChE inhibitor

Irreversible AChE inhibition

volatile; Chemical warfare agent