Cholinergic stimulants indirect-acting

FIGURE 19-1 T Mechanism of action of cholinergic stimulants. Direct-acting stimulants bind directly to the postsynaptic cholinergic receptor. Indirect-acting stimulants inhibit the cholinesterase enzyme, thus allowing acetylcholine to remain in the synaptic cleft. 

Indirect-acting stimulants increase activity at cholinergic synapses by inhibiting the acetylcholinesterase enzyme.21 This enzyme is normally responsible for destroying acetylcholine after this neurotransmitter... 

Cholinergic medication (cholinesterase inhibitors, anticholinesterase) has either a direct- or indirect-acting effect on receptor sites. Direct and indirect effects inhibit the action of the enzyme cholinesterase (acetylcholinesterase). By inhibiting cholinesterase, more acetylcholine is available to stimulate the receptor and remains in contact with the receptor longer. 

Dopamine acts on G-protein-coupled receptors belonging to the D1 -family of receptors (so-called D1-like receptors , or DlLRs, comprised of Dl- and D5-receptors), and the D2-family of receptors ( D2-like receptors , or D2LRs comprised of D2-, D3- and D4-receptors). Dl LRs stimulate adenylate cyclase activity and, possibly, also phosphoinosit-ide hydrolysis, while D2LRs reduce adenylate cyclase activity. In the striatum, DlLRs are predominately associated with medium spiny neurons of the direct pathway, while D2LRs have been found as autoreceptors on dopaminergic terminals, as heteroreceptors on cholinergic interneurons, and on indirect pathway neurons. In the SNr, DlLRs are located on terminals of the direct pathway projection, while D2LRs appear to function as autoreceptors. 

These four alkaloids stimulate smooth muscles innervated by postgan-ghonic cholinergic nerves. The first three act directly, but the action of physostigmine is an indirect one through cholinesterase inhibition. Moreover, the actions of physostigmine are more complex, and its effects, particularly in the intact animal, more difficult to predict. None of these alkaloids are of clinical importance as oxytocics. 

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