Quaternary ammonium salts curare-like

It has long been known that quaternary ammonium salts can exert a curare-like action, and in recent years much attention has been given to the synthesis and pharmacological testing of such products work on this subject up to 1936 has been reviewed by Ing, and more recently a theoretical discussion of the relationship between structure and action in drugs of this type has been provided by Holmes, Jenden and Taylor.Chase, Lehmann and Yonkmann have compared the action of quaternary salts of quinine with that of -erythroidine hydrochloride and of dihydro- -erythroidine hydrobromide. Quinine ethochloride shows marked curariform action of short duration. ... 

Barlow RB, Ing HR (1948) Curare-like action of polymethylene bis-quaternary ammonium salts. Br 1 Pharma Chemother 3 298-304... 

Curare-like muscle relaxants quaternary ammonium salts... 

The production of a quaternary ammonium salt from a tertiary amine and an alkyl halide forms the synthetic route to decamethonium, the first of a range of synthetic muscle relaxants having an action like the natural materials found in the arrow-poison curare. Decamethonium is actually a di-quaternary salt, as are more modem analogues, such as suxamethonium. Suxamethonium superseded decamethonium as a drug because it has a shorter and more desirable duration of action in the body. This arise because it can be metabolized by ester-hydrolysing enzymes (esterases) (see also Box 6.9). 

Curare-like muscle relaxants act by blocking acetylcholine receptor sites, thus eliminating transmission of nerve impulses at the neuromuscular junction. There are two acetylcholine-like groupings in the molecules, and the drugs, therefore, probably span and block several receptor sites. The neurotransmitter acetylcholine is also a quaternary ammonium compound. The natural material present in curare is tubocurarine, a complex alkaloid that is a mono-quaternary salt. Under physiological conditions, the tertiary amine will be almost completely protonated (see Section 4.9), and the compound will similarly possess two positively charged centres. 

The alkaloid content of curare is from 4% to 7%. The most important constituent in menispermaceous curare is the bis-benzyltetrahydroisoquinoline alkaloid (+)-tubocurarine (Figure 6.48). This is a monoquaternary ammonium salt, and is water soluble. Other main alkaloids include non-quaternary dimeric structures, e.g. isochondrodendrine and curine (bebeerine) (Figure 6.48), which appear to be derived from two molecules of (R)-N-methylcoclaurine, with the former also displaying a different coupling mode. The constituents in loganiaceous curare (from calabash curare, i.e. Strychnos toxifera) are even more complex, and a series of 12 quaternary dimeric strychnine-like alkaloids has been identified, e.g. C-toxiferine (toxiferine-1) (see page 359). 

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See also in sourсe #XX -- [ ]

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