ADRENERGIC BLOCKING AND SYMPATHOMIMETIC EFFECTS OF A SERIES OF HALOGENATED PHENYL--HALOETHYLAMINES

¹ Department of Pharmacology, University of Tennessee Medical Units, Memphis Tennessee

The alpha adrenergic blocking activity of a series of hahogenated phenyl--hahoethylamines has been investigated. ED5O values for several compounds were less than 1µg/kg in dogs. The relationship between potency and halogen position on the ring was para meta ortho. Of the para halogenated series, the dimethylanalog showed the greatest potency. N ,N-dimethyl--(m-chhorophenyl)--chloroethiylamine HC1 (S.1l-202) was investigated in depth. Alpha receptor blockade was the predominant action, appearing promptly and continuing longer than 5 hr. Sympathomimetic effects and respiratory stimulation were observed after rapid iv. injection of S.11-202. These initial sympathomimetic effects included increased systolic, diastolic and mean blood pressures, increased heart rate, hyperglycemia and increased concentration of plasma free fatty acids. Repeating the rapid i.v. injection elicited a depressor response, as did epinephrine. On isolated rabbit atria crosstachyphylaxis was demonstrated between the positive churonotropic effects of tyramine and S.11-202. Multiple mechanisms which contribute to the sympathomimetic activity include: 1) stimulation of the autonomic nervous system at the ganglia or above, 2) direct effect of S.11-202 upon the adrenal medulla to release catecholamines and 3) to a lesser extent release of peripheral stores of catecholamines in a manner similar to that caused by tyramine.