Mode of Action of Cholinomimetic Drugs

MODE OF ACTION OF CHOLINOMIMETIC DRUGS

Direct-acting cholinomimetic agents bind to and activate muscar-inic or nicotinic receptors (Figure 7–1). Indirect-acting agents produce their primary effects by inhibiting acetylcholinesterase, which hydrolyzes acetylcholine to choline and acetic acid (see Figure 6–3). By inhibiting acetylcholinesterase, the indirect-acting drugs increase the endogenous acetylcholine concentration in syn-aptic clefts and neuroeffector junctions. The excess acetylcholine, in turn, stimulates cholinoceptors to evoke increased responses. These drugs act primarily where acetylcholine is physiologically released and are thus amplifiers of endogenous acetylcholine.

Some cholinesterase inhibitors also inhibit butyrylcholinesterase (pseudocholinesterase). However, inhibition of butyrylcholinest-erase plays little role in the action of indirect-acting cholinomimetic drugs because this enzyme is not important in the physiologic ter-mination of synaptic acetylcholine action. Some quaternary cholin-esterase inhibitors also have a modest direct action as well, eg, neostigmine, which activates neuromuscular nicotinic cholinocep-tors directly in addition to blocking cholinesterase.