Muscarinic Receptors

The Central and Peripheral Activity of Acetylenic Amines Related to Oxotremorine

“…From this evidence it may perhaps be concluded that the structure ofthe tremorogenic site located in the central nervous system very closely resembles that of the peripheral postganglionic parasympathetic acetylcholine receptor. The structure of this peripheral receptor has been discussed by Beckett, Harper, Clitherow & Lesser (1961), Beckett, Harper & Clitherow (1963), Waser (1961) and Belleau & Puraneft (1963) with particular reference to the activity of muscarine, muscarone and the highly active quaternary salts of 5-dimethylaminomethyl-2-methyl-1,3-dioxolane. Beckett et al (1963) have suggested that muscarinic drugs may interact with the receptor at an anionic site (site 1), and a cationic site (site 2), separated by 3 to 3.5 A, and also at a third site located at a distance of 5 to 7 A from the anionic site.…”

Conformations of erythro- and threo-Dimethylacetylcholine Iodides in the Solid State

“…Keyphrases 0 eryrhro-a,@-Dimethylacetylcholine iodides-structure determinations 0 fhreo-a,@-Dimethylacetylcholine iodidesstructure determination 0 Conformation, structural-erythro-and threo-a,j+dirnethylacetylcholine 0 X-ray crystallography-structure determination Substitution of methyl groups on the a-and/or pcarbons of the acetylcholine molecule (ACh) has dramatic effects on both the muscarinic activity of the analog and the hydrolysis rate of the molecule in the presence of acetylcholinesterase (AChE) (1,2). Pharmacological studies (2) on the erythro( *)and threo( f )a,@-dimethylacetylcholine compounds indicated that the racemic erythro-material is over 300 times more potent as a muscarinic agent than the racemic threo-compound.…”

The Interaction of Muscarinic Drugs With the Postganglionic Acetylcholine Receptor

“…Waser (1961), however, has claimed that this explanation by Beckett et al (1961Beckett et al ( , 1963 does not account for the low and inverse stereospecificity of muscarone compared with muscarine. He preferred to consider that muscarinic activity in muscarine-like compounds depends mainly on the quaternary group and a nucleophilic group which in muscarine is the ether oxygen atom and in muscarone is the carbonyl group.…”

“…From a consideration of the chemical and pharmacological properties of muscarine and muscarone, Beckett, Harper, Clitherow & Lesser (1961) and Beckett, Harper & Clitherow (1963) have proposed a tentative picture of the muscarinic receptor based on a three-point attachment of the molecules to the receptor surface. They suggested that the three groups involved in the interaction of muscarine with the receptor are the quaternary ammonium group, the ether oxygen atom and the hydroxyl group; in muscarone, the quaternary group, the ether oxygen atom and the ketonic carbonyl group are involved.…”