Effects of deuterium substitution on the chronotropic responses to some sympathomimetic amines in the isolated rat atria |
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Authors: | Stella Maris Celuch Augusto V. Juorio |
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Affiliation: | (1) Psychiatric Research Division, Saskatchewan Health, Cancer and Medical Research Building, University of Saskatchewan, S7N OWO Saskatoon, Saskatchewan, Canada |
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Abstract: | 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: ,,d2--phenylethylamine; ,,,-d4-p-tyramine; ,,,-d4-m-tyramine; ,,-d3-p-octopamine. In contrast, ,,-d3-noradrenaline and ,,-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 -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 ,,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 - or the -carbon, can alter some other mechanisms in addition to the enzymatic deamination.Career Investigator on leave of absence from the Consejo de Investigaciones Cientificas y Técnicas, ININFA, Junín 956, 5°P, RA-1113 Buenos Aires, ArgentinaSend offprint requests to S. M. Celuch |
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Keywords: | Isolated rat atria Deuterated noradrenaline Deuterated /content/r154743853m887wr/xxlarge946.gif" alt=" beta" align=" MIDDLE" BORDER=" 0" >-phenylethylamine Deuterated p- and m-tyramine Deuterated p- and m-octopamine |
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