CHOLINOMIMETICS

Introduction: The actions of acetylcholine released from autonomic and somatic motor nerves are terminated by enzymatic hydrolysis of the molecule. Hydrolysis is accomplished by the action of the enzyme acetylcholinesterase, which is present in high concentrations in cholinergic synapses. The indirect-acting cholinomimetics have their primary effect at the active site of this enzyme, although some also have direct actions at nicotinic receptors. Receptors in the Central nervous system

Structure: There are three chemical groups of cholinesterase inhibitors: (1) simple alcohols bearing a quaternary ammonium group, such as, edrophonium; (2) carbamic acid esters of alcohols having quaternary or tertiary ammonium groups (carbamates, such as, neostigmine); and (3) organic derivatives of phosphoric acid (organophosphates, such as, echothiophate). Toxicity due toorganophosphates

Pharmacodynamics: Mechanism of Action: Acetylcholinesterase is the primary target of these drugs, but butyrylcholinesterase is also inhibited. Acetylcholinesterase is an extremely active enzyme. In the initial catalytic step, acetylcholine binds to the enzyme’s active site and is hydrolyzed, yielding free choline and the acetylated enzyme. In the second step, the covalent acetyl-enzyme bond is split, with the addition of water (hydration). All the cholinesterase inhibitors increase the concentration of endogenous acetylcholine at cholinoceptors by inhibiting acetylcholinesterase. The organophosphate inhibitors are sometimes referred to as “irreversible” cholinesterase inhibitors, and edrophonium and the carbamates are considered “reversible” inhibitors because of the marked differences in duration of action. However, the molecular mechanisms of action of the three groups do not support this simplistic description.

RELATED;

1.  THE NERVE IMPULSE PROPAGATION

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