RESPONSES TO SYMPATHOMIMETIC AMINES AFTER DIBENAMINE BLOCKADE

¹ Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, Michigan
² Department of Pharmacology, University of Utah College of Medicine, Salt Lake City, Utah

The ability of Dibenamine to block the blood pressure rise and the contraction of the denervated nictitating membrane induced by a series of 29 sympathomimetic agents has been studied in cats. Dibenamine completely blocks the contraction of the denervated nictitating membrane induced by any of the sympathomimetics tested. Even the "depressor" amines, including isopropylnorepinephrine, exerted a considerable "excitatory" effect on the nictitating membrane. The depressor/pressor ratio (relative depressor activity) of the phenethylamine sympathomimetics was found to be increased by the presence of phenolic hydroxyl groups in the 3 and 4 positions, by alkyl substituents on the nitrogen or on the -carbon and to a slight extent by a -alcoholic hydroxyl group. At least one phenolic hydroxyl and one of the alkyl substituents must be present to provide any considerable depressor activity when the amine is administered in doses equipressor with 1.0 microgm./kgm. of epinephrine. Administration of large doses of the amines after Dibenamine blockade revealed a significant depressor component in the action of agents which produced no "reversal" in smaller doses.

The complexity of the blood pressure response to sympathomimetic agents is stressed and it is pointed out that the reported inability of Dibenamine and other adrenergic blocking agents to "reverse" or abolish the vasopressor response to certain sympathomimetics may be largely due to differences in properties of the stimulating agents other than vasoconstrictor activity, which is the only portion of the response which adrenergic blocking agents can influence.