THE HEMODYNAMIC EFFECTS OF HYPOTENSIVE DRUGS IN MAN. I. VERATRUM VIRIDE

Dale in 1906 recognized the sympatholytic ac-tivity of crude extracts of ergot as well as their property of direct stimulation of smooth muscle, including that of the blood vessels (1). Despite their sympatholytic effects their direct vasocon-strictor action prevented significant lowering of arterial pressure. Later chemical purification of the crude drug resulted in the isolation of five alkaloids: ergot-amine (2), ergobasine (3), ergokryptine, ergocor-nine and ergocristine (4). The basic chemical structure of these compounds was clarified by Jacobs and Craig (5) who demonstrated the pres-ence of lysergic acid in all of the alkaloids (6). By hydrogenating the reducible double bond of the lysergic acid component of four of these alka-loids, Stoll and Hofmann (7) in 1943 produced a new series of compounds, dihydroergotamine, di-hydroergocristine, dihydroergocornine (DHO-180) 5 and dihydroergokryptine (DHK-135).5 Pharmacological studies in animals (8) indicated that these modified compounds have enhanced sympatholytic and adrenolytic properties but little or no direct constrictor action on smooth muscle. In addition, they are hypotensive, this effect be-ing mediated at least in part via the central nervous system (9). In man DHO and DHK in non-toxic doses have sympatholytic and hypotensive prop