Muscarinic agents

Tlal LJ, Forreest M, Loft FI, Lu-25-109, a muscarinic agent, fails to improve cognition in Alzheimers disease, Neurology 54 421-426, 2000. 

Anti-malarials Anti-migraine agents Anti-muscarinic agents... 

Nilsson, B. M. Ringdahl, B. Hacksell, U. Derivatives of the muscarinic agent N-methyl-N-(l-methyl-4-pyrrolidino-2-butynyl)acetamide. 

In summary, different muscarinic agents show promise as potential new treatments of schizophrenia. Potential treatment targets for these agents include both positive and negative symptoms as well as cognitive symptoms. However, more studies are necessary before the utility of a muscarinic approach to the treatment of schizophrenia can be assessed. 

In the same study EHT predictions were reported for the potent muscarinic agents muscarine, Figure 2, and muscarone, Figure 3(8). The experimental evidence available for comparison are x-ray analyses of the muscarine (10) and muscarone (80) crystals, with which the predicted conformations agree. 

Superpositioning these three potent muscarinic agents, in their preferred conformations resulted in the observation of a common pattern of similarly charged structural features. The pattern, Figure 4, was proposed as the muscarinic pharmacophore (8). This pattern, predicted from theoretical considerations, bears a striking similarity to the muscarinic pharmacophore proposed by Beckett based on extensive structure—activity studies... 

Calculations on oxotremorine (15), presumed to be a CNS muscarinic agent, revealed that this molecule, in its predicted conformation (Figure 5) mimicks this predicted muscarinic pharmacophore. The assumption is made that the electronic character of the triple bond is the receptor equivalent of the ether oxygen atom in acetylcholine as proposed by Bebbington (16). These calculations support his proposal and reveal how oxotremorine may meet the structural requirements of a muscarinic agent. 

Erickson KA, Schroeder A. Direct effects of muscarinic agents on the outflow pathways in human eyes. Invest Ophthalmol Vis Sci 2000 41 1743-1748. 

Chemical/Pharmaceutical/Other Class Anti-muscarinic agent Anticholinergic agent... 

The crystal structures of certain nicotinic agents, for example, acetyl a-methylcholine (32)and lactoylcholine (17in Table 2.1), have torsion angle (rg and T3) features similar to most muscarinic agents (262). In eontrast, some cyclic analogs of aryl choline ethers exhibit maximum nicotinic effects when the Tg is antiplanar ("transoid") (98). 

The muscarinic actions of acetylcholine can be either stimulatory or inhibitory. Acetylcholine stimulates secretion and contraction of the gut, but it inhibits the contraction of the heart and relaxes the smooth muscle of blood vessels. Acetylcholine can inhibit adenylate cyclase and activate guanylate cyclase. In the cortical neurones, muscarinic agents cause a slow depolarization mediated by closing potas-... 

Structure-activity relationships among muscarinic agents (or cholinergics) indicate the ex-... 

Carbachol (Figure 3.12), and the closely related bethane-chol, is a powerful cholinergic agent (used to induce miosis). Its structure is similar to that of choline and its precursor, DMAE. Other muscarinic agents (e.g. pilocarpine), have a completely different chemical structure to choline. 

In ntro fiinaional activity of McN-A-343 analogues at Mj receptors in rabbit vas deferens (RVD), M2 receptors in guinea-pig atria (GPA) and M3 receptors in guinea-pig ileum (GPI). Abbreviations for the muscarinic agents are explained in the legend of Figure 1... 

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