Pharmacologically active amine salts

Owing to the late development of fast, small, and inexpensive computers, little work was performed on pharmaceutical samples until the 1980s. In 1966, many pharmacologically active amine salts were investigated both in solid state and in solution. Two drugs were quantified in 1967 allylisopropylacetureide and phenacetin were dissolved in chloroform and simultaneously quantified at 1983 and 2019nm, respectively. 

In 1966, Sinsheimer and Keuhnelian investigated a number of pharmacologically active amine salts both in solution and in the solid state [12]. In 1967, Oi and Inaba quantified two drugs allylisopropylacetureide (AL) and phenacetin (PH) [13]. Samples were dissolved in chloroform and quantified at 1983 nm for AL and 2019 nm for PH. 

Finally, it should be mentioned that the curare alkaloids - as is generally known - are quaternary salts and due to their strong hydrophilicity they have to be administered parenterally. In contrast, the Erythrina alkaloids are all tertiary amines and therefore they are able to develop their pharmacological activities upon oral administration. 

An important factor in stimulating the early structural studies of Erythrina alkaloids during the 1940 s was the discovery of their curariform activity (cf. Craig 1955) this appears to be associated with the spiroamine moiety, and in contrast with the curare alkaloids, which are quaternary salts, the Erythrina alkaloids are all tertiary amines. Many other types of pharmacological activity have also been discovered with Erythrina alkaloids, e.g. sedative, hypotensive, CNS depressing, laxative and diuretic properties. 

The phenethylamine homologue of TMA-6 is well known, but is virtually unexplored pharmacologically. The above benzaldehyde with nitromethane in glacial acetic acid containing ammonium acetate gave the appropriate beta-nitrostyrene as yellow crystals with a mp 177-177.5 °C. This, with LAH in ether, gave 2,4,6-trimethoxyphenethylamine (2,4,6-TMPEA, or 2C-TMA-6) as the picrate salt (mp 204-205 °C) or the hydrochloride salt (mp 234-235 °C). It has been shown not to be a substrate to the soluble amine oxidase from rabbit liver, a property it shares with mescaline, but whether it is or is not active in man is at present unknown. 

Imipramine is a 10,11 -dihydrodibenzazepine tertiary amine TCA (Fig. 21.15) that is marketed as hydrochloride and pamoate salts, both of which are administered orally. Although the hydrochloride salt may be administered in divided daily doses, imipramine s long duration of action suggests that the entire oral daily dose may be administered at one time. On the other hand, imipramine pamoate usually is administered as a single daily oral dose. Imipramine preferentially inhibits 5-HT reuptake over NE however, the formation of its N-desmethyl metabolite removes whatever 5-HT activity imipramine had, with the net result of enhanced noradrenergic activity from inhibition of NE reuptake at the presynaptic neuronal membrane. Imipramine shares the pharmacological and adverse-effect profile of the other tertiary TCAs. 

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