Indirect-gedragende Cholinergische Agonisten: Chemie en Structuur-Activiteitsrelatie

Indirect-acting cholinergic agonists bind to AChE enzymes at the synaptic cleft and inhibit ACh hydrolysis. This results in increased concentration of ACh at the synapse, indirectly enhancing cholinergic action.

In general, they are classified as either reversible or irreversible inhibitors based on their duration of action.

Reversible inhibitors are short- and intermediate-acting agents.

Short‐acting agents are simple alcohols bearing quaternary ammonium groups such as edrophonium.

Intermediate‐acting agents include carbamic esters such as neostigmine and physostigmine.

Neostigmine is a carbamate bearing a quaternary ammonium group, while physostigmine is a naturally occurring carbamate with a tertiary amine group.

Irreversible inhibitors include organophosphates. They are phosphoric acid derivatives with multiple substituents, where one of the substituents functions as a labile group.

For instance, echothiophate consists of two alkoxy groups and one thiocholine group. Sarin, a nerve gas, has one alkoxy, one alkyl, and one halogen group. Here, the thiocholine and halogen are labile groups.