SPECIFICITY AND POTENCY OF ARYL-HALOALKYLAMINE ADRENERGIC BLOCKING DRUGS AS DETERMINED ON ISOLATED SEMINAL VESICLES OF GUINEA PIGS

¹ Department of Physiology, Boston University School of Medicine, Boston

The relative ability of various aryl-2-haloalkylamine adrenergic blocking drugs to block the spasmogenic effects of equi-effective doses of epinephrine, norepinephrine, histamine, and acetylcholine has been studied on the isolated guinea pig seminal vesicle. The results have been interpretated to indicate the relative potency of the antagonists with respect to antagonism of a given spasmogen, and, also, the relative specificity a single antagonist exhibits in antagonizing the various spasmogens.

All aryl-haloalkylamines studied were found to block the effects of epinephrine, nor-epinephrine, and histamine on the seminal vesicle. The effect of the blocking agents on the acetylcholine induced spasm was inconstant; N-ethyl-N-(2-chloroethyl)-benzhydrylamine·HCl (SY-2) and N-(2-chloroethyl)-dibenzylamine· HCl (Dibenamine) had no effect in non-spasmogenic amounts. However, N-ethyl-N-(2-bromoethyl)-1-naphthalene-methylamine-HBr (SY-28) and 2-(2-biphenyloxy)-2'chlorotriethylamine·HCl (SY-8) antagonized acetylcholine, albeit in doses considerably above those required of atropine sulfate; and N-ethyl-N-(2-chloroethyl)-9-fluorenamine·HCl (SY-21) potentiated acetylcholine-induced spasm.

N-ethyl-N-(2-chloroethyl)-9-fluorenamine (SY-21) was five times as potent as Dibenamine in antagonizing epinephrine, although N-ethyl-N-(2-chloroethyl)-benzhydrylamine (SY-2) was more discriminating in this regard since 44 times the quantity of drug was required to block histamine to the same degree as epinephrine. In this respect SY-21 and Dibenamine were 20 and 13 times as discriminating, respectively.

No parallelism existed among these drugs between the relative order of potency with respect to antagonism of epinephrine, histamine, or acetylcholine, while such a relationship was found to exist between epinephrine and norepinephrine.

The specificity demonstrated with atropine against acetyicholine and pyranisamine against histamine agree with those reported by Schild, who employed the guinea pig ileum. The use of the seminal vesicle, however, has the added advantage in that a broader spectrum of drug antagonism can be studied on a single test object.