Muscarinic receptors subgroups

Table 8-1 Muscarinic Receptor Subgroups and Their Antagonists. ...

Table 8-1. Muscarinic Receptor Subgroups and Their Antagonists. (Acronyms Identify Selective Antagonists Used in Research Studies Only.) ...

In the periphery, some of the primary triggers for these processes have been identified. Acetylcholine seems to be one such factor because stimulation of preganglionic nerves in vivo increases enzyme activity. However, nicotinic and muscarinic receptor antagonists do not completely prevent this increase. The residual activation is attributed to peptides of the secretin-glucagon subgroup, including VIP and secretin both these peptides activate cAMP synthesis. Purinergic transmitters could also be involved. 

Many first-generation agents, especially those of the ethanolamine and ethylenediamine subgroups, have significant atropine-like effects on peripheral muscarinic receptors. This action may be responsible for some of the (uncertain) benefits reported for nonallergic rhinorrhea but may also cause urinary retention and blurred vision. 

Atropine does not distinguish between the Mi, M2, and M3 subgroups of muscarinic receptors. In contrast, other antimuscarinic drugs have moderate selectivity for one or another of these subgroups... 

One of the possible advantages to a therapeutic strategy for Alzheimer s disease or other deficits in memory and learning using acetylcholine-releasing agents is that such a process would seem to permit stimulation of both nicotinic and muscarinic receptors in the. brain and to permit stimulation of all subgroups of acetylcholine receptors. 

A. Classification Muscarinic agonists are parasympathomimetic, ie, they mimic the actions of parasympathetic nerve stimulation. Five subgroups of muscarinic receptors have been identified (Table 7-3), but selective agonists for these receptor subtypes are not available for clinical use. Nicotinic agonists are classified on the basis of whether ganglionic or neuromuscular stimulation predominates however, agonist selectivity is very limited. On the other hand, relatively selective antagonists are available for the two nicotinic receptor types (Chapter 8). 

The issue of drug selectivity is related closely to the fact that many receptor populations can be divided into various subtypes according to specific structural and functional differences between subgroups of the receptor. A primary example is the cholinergic (acetylcholine) receptor found on various tissues throughout the body. These receptors can be classified into two primary subtypes muscarinic and nicotinic. Acetylcholine will bind to either subtype, but drugs such as nicotine will bind preferentially to the nicotinic subtype, and muscarine (a toxin found in certain mushrooms) will bind preferentially to the muscarinic subtype. 

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