PT - JOURNAL ARTICLE AU - J. L. Schmidt AU - W. W. Fleming TI - THE STRUCTURE OF SYMPATHOMIMETICS AS RELATED TO RESERPINE INDUCED SENSITIVITY CHANGES IN THE RABBIT ILEUM DP - 1963 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 230--237 VI - 139 IP - 2 4099 - http://jpet.aspetjournals.org/content/139/2/230.short 4100 - http://jpet.aspetjournals.org/content/139/2/230.full SO - J Pharmacol Exp Ther1963 Feb 01; 139 AB - Variations in chemical structure among 21 sympathomimetics have been correlated with sensitivity changes to the compounds in the rabbit ileum following reserpine pretreatment. The magnitude of the increase or decrease in sensitivity varies greatly according to the chemical structure. The relationship of sensitivity changes to direct and indirect action is discussed. On the basis of the results, it is hypothesized that sympathomimetics do not fall into three classes, direct acting, indirect acting, and mixed direct and indirect acting, but into a spectrum of substances, all of which may have both direct and indirect action and differ only in the ratio of direct to indirect action. The following conclusions have been made regarding the relationship of chemical structure to direct action: (1) The para and meta hydroxyl groups are not both essential to direct action. (2) Dichloro substitution for the hydroxyl groups on the catechol nucleus only slightly reduces direct action. (3) The beta hydroxyl group is important for direct action. (4) Substitution of a meta methoxy for a meta hydroxyl group profoundly reduces direct action; however, the meta methoxy group results in greater direct action than no meta substitution at all. The probability that all sympathomimetics possess indirect action is discussed. Tyramine, methoxamine, phenylethylamine and B.W. 37, which represent nearly pure indirect action, depend upon the available tissue stores of sympathomimetic amines for their action. The ratio of indirect to direct activity which a particular compound may possess determines its position in the spectrum.