A study of the biochemical pharmacology of 3,5-ethoxy-4-aminomethylpyridine (B24), a novel amine oxidase inhibitor with selectivity for tissue bound semicarbazide-sensitive amine oxidase enzymes.
The pycolylamine derivative, 3,5-ethoxy-4-aminomethylpyridine (B24) is a novel amine oxidase inhibitor with selectivity for semicarbazide-sensitive amine oxidase enzymes (SSAO). If selective enough it could be of use in studies of the relative importance of tissue bound SSAO and other amine oxidase enzymes, such as plasma SSAO (BAO), monoamine oxidase (MAO) and diamine oxidase (DAO) in the inactivation of endogenous and exogenous amines. The inhibition of the SSAO of brown adipose tissue of the rat by B24 was mixed and time dependent, with an IC(50) value against 10 ?M benzylamine of 0.3 ?M B24 was also potent on pig plasma BAO, where its effect was also mixed but fully reversible by dialysis, with an IC(50) of 0.17 ?M. These values contrast with a K(i) of 800 ?M for rat liver mitochondrial MAO-A and an IC(50) of greater than 1 mM for the deamination of 2-phenylethylamine (mainly MAO-B). DAO and lysyl oxidase were also very insensitive to inhibition by B24. Addition of B24 to the fluid perfusing the isolated mesenteric arterial bed of the rat significantly reduced the deamination of both benzylamine and tyramine, indicating that it was able to inhibit SSAO in situ. It appears that B24 is a selective inhibitor of both tissue bound and plasma SSAO, which should be an important aid in clarifying the physiological rôles of the various SSAO enzymes.
Banchelli
G
G
Department of Clinical and Preclinical Pharmacology, University of Florence, Viale G.B. Morgagni, 65, 50134 Florence, Italy.
Buffoni
F
F
Elliott
J
J
Callingham
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