Pharmacologically active cholines

A pharmacologically active choline ester and other substances in the garden tiger moth, Arctia caja (L.). Proceedings of the Royal Society of London 152 225-262. 

Whittaker, V. P., Acrylcholine A new naturally occurring pharmacologically active choline ester from Buccinum undatum. Biochem. Pharmacol 1, 342-346 (1958). 

Whittaker, V.P., 1960. Pharmacologically active choline esters in marine gastropods. In Biochemistry and Pharmacology of Compounds Derived from Marine Organisms. Ann. N.Y. Acad. Sci., 90 695—705. 

The spleen in some species contains relatively large amounts of propionyl-choline . This fact, together with the presence of butyrocholinesterase in the central nervous system and the pharmacological activity of the choline esters, suggests the possibility that substances related to acetylcholine may also participate in the processes of synaptic transmission. Although choline esters other than acetylcholine, as well as other substances with acetylcholine-like activity, have been reported to occur in the brain " , pharmacological and biochemical analyses of brain extracts have failed to confirm these claims " . Similar reports of the existence of acetylcholine-like substances in peripheral nerve extracts have also proved impossible to confirm . The physiological substrate of pseudocholinesterase in the nervous system—if, indeed, it is not acetylcholine— remains unknown. Attempts to solve the problem by differential inhibition of the two cholinesterases in the brain have so far proved unsuccessful. 

Welch AD, Roepke MH. A comparative study of choline and certain of its analogues. I. The pharmacological activity of... 

A substance with similar pharmacological activity could be obtained from a choline plasmalogen prepared from heart. The choline plasmalogen is now known to be glycerol l-alkenyl-2-acyl-3-phosphorylcholine (II) [see Gottfried and Rapport (1962), for references]. 

This view was supported by the observation that choline on treatment with nitric acid yielded a product having a pharmacological action similar to that of muscarine as known up to that time. Comparison of the natural and artificial products by Bohm showed that the former was much more active than the latter and that its action was antagonised by atropine, whilst the artificial muscarine had a curare-like action on the atropinised frog. Later, Nothnagel investigated the action of... 

Choline esters are poorly absorbed and poorly distributed into the central nervous system because they are hydrophilic. Although all are hydrolyzed in the gastrointestinal tract (and less active by the oral route), they differ markedly in their susceptibility to hydrolysis by cholinesterase in the body. Acetylcholine is very rapidly hydrolyzed (see Chapter 6 Introduction to Autonomic Pharmacology) large amounts must be infused intravenously to achieve concentrations high enough to produce detectable effects. A large intravenous bolus injection has a brief effect, typically... 

Bethanechol Chloride, USP. Bethanechol. jS-mcthyl-choline chloride carbamate. (2-hydroxypropyl)trimethylam-monium chloride carbamate, carbamylmelhylcholinc chloride (Urecholinc), is nonspecific in its action on muscarinic receptor. subtypes but appears to be more effective at eliciting pharmacological action of M> receptors. It has pharmacological properties similar to those of methacholinc. Both are esters of nicthylcholine and have feeble nicotinic activity. Bethanechol is inactivated more slowly by AChE in vivo than is mcthacholine. It is a carbamyl ester and is expected to have stability in aqueous solutions similar to that of carbachol. 

Qualitatively, choline has the same pharmacological actions as acetylcholine, but it is far less active at most sites (58). However, choline has been reported (34) to be a full agonist at one nicotinic receptor subtype, and at some other nicotinic subtypes it can act as a partial agonist or a coagonist. 

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). 

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