ISSN:
1432-1912
Keywords:
Isolated rat atria
;
Deuterated noradrenaline
;
Deuterated β-phenylethylamine
;
Deuterated p- and m-tyramine
;
Deuterated p- and m-octopamine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary In spontaneously beating rat atria the potencies for the chronotropic effects of the following deuterated phenylethylamine derivatives were higher than the potencies of the corresponding non-substituted (protio-) amines: α,α,d2-β-phenylethylamine; α,α,β,β-d4-p-tyramine; α,α,β,β-d4-m-tyramine; α,α,β-d3-p-octopamine. In contrast, α,α,β-d3-noradrenaline and α,α,β-d3-m-octopamine were equipotent with the corresponding protio-amines. Experiments performed in atria depleted of endogenous noradrenaline by pretreatment with reserpine and in atria exposed to the monoamine oxidase (MAO) inhibitor pargyline indicated: a. p-octopamine had both direct and indirect effects, but the chronotropic responses to p-octopamine in tissues with normal MAO activity depended mostly on the direct action of the amine; deuterium substitution enhanced the indirect component of action of p-octopamine; b. m-octopamine possessed considerable indirect effects while d3-m-octopamine behaved as an amine of direct action. The substitution of deuterium for hydrogens in the α-carbon of the alkyl-side chain of phenylethylamines decreases the rate of deamination by MAO. Therefore, the results obtained with all the amines, except for m-octopamine and α,α,p-d3-m-octopamine, could be interpreted in terms of the direct, indirect or mixed action of those compounds and/or of the influence that MAO activity has on the chronotropic responses to these amines. The results obtained with protio-and deuterio-m-octopamine suggested that deuterium substitution, either at the α- or the β-carbon, can alter some other mechanisms in addition to the enzymatic deamination.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00164871
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