Cholinergic agonists structures

Sauerberg, R, Kindtler, J. W., Nielsen, L., Sheardown, M. J., Honord, T. Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-l,2,4-oxadiazol-5-yl)l,2,5,6-tetrahydropyridine type synthesis and structure-activity relationships. J. Med. Chem. 1991, 34, 687-692. 

Table 8-2 illustrates data from early work attempting to evaluate the structural requirements of cholinergic agonist activity directly and thereby indirectly glean some insight into the receptors geometrical parameters for active compounds. These types of data, when... 

The profound muscarinic activity of the alkaloid muscarine provided substantial rationale for synthesizing ethers of choline. Muscarine, which is obtained from the red variety of mushroom Amanita muscaria) and other mushrooms is one of the oldest known cholinergic agonists and is the compound tor which muscarinic receptors were named. It was used in many pharmacological experiments during the latter 19th century and the early part of the 20th century, and its use preceded the discovery and chemical characterization of acetylcholine (2). The chemical structure of muscarine (see above), however, was not completely characterized until 1957. Muscarine possesses three chiral centers (C2, C3, and C5). 

Acetylcholine Both anticholinergics (antagonists) that block the cholinergic receptor and acetylcholinesterase inhibitors (potentiate acetylcholine) are in use today and are based on the acetylcholine structure. Because of the efficiency of acetylcholinesterase, it has proved more productive to inhibit the enzyme that hydrolyzes this neurotransmitter rather than develop cholinergic agonists. 

The intrinsic complexity and the multiplicity of cholinergic receptors became evident upon elucidation of their primary structures. In the CNS, at least nine different sequences of a subunits and three different sequences of (3 subunits of the nicotinic receptor have been identified [10, 11]. Expression of the cloned genes encoding certain subunit combinations yields functional receptors with different sensitivities toward various toxins and agonists. 

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