448 YOUNGKEN, JR. 



agents in the treatment of angina and arterial hypertension. However, an 

 intensive re-investigation of one well-known plant drug, Veratrum viride, or 

 green hellebore, and a similar study of two lesser-known plant drugs, Ammi 

 visnaga (Khella) and Rauwolfia species, have resulted in several new and 

 useful pharmaceuticals of the hypotensive class. Certainly the supremacy of 

 the nitrites and/or nitrates in this field has now been challenged. Veratrum 

 and Rauwolfia represent botanical crude drugs which have been employed 

 in folklore domestic and foreign medicine for centuries and for a variety of 

 purposes. Among these, for example, the roots and rhizomes of Veratrum 

 viride, a plant indigenous to parts of North America and Europe, have had 

 application in galenical forms as a bird poison, insecticide, emetic, cardiac 

 tonic, and use in eclampsia; Khella, the dried fruit of Ammi visnaga, a plant 

 which grows wild in the eastern Mediterranean basin, has been used for 

 renal colic and as a diuretic. One of its crystalline components, khellin, was 

 reported in 1930 to have direct relaxing action on visceral and coronary 

 artery smooth musculature. The dried roots of Rauwolfia serpentina, a small 

 shrub of India, have been used empirically by people of India for a large 

 variety of conditions, such as in the treatment of snake bites, insanity, high 

 blood pressure, and cardiac disease. Some of its alkaloid principles were first 

 isolated by the Indian chemist, Siddiqui, in 1931. These older botanicals have 

 been most extensively re-investigated chemically and pharmacologically since 

 about 1947. As a result we now have numerous modern pharmaceutical prep- 

 arations of these once obsolete drugs, preparations containing crude drug 

 materials and their isolated constituents. Among the latter constituents are 

 the alkaloids jervine, cevine, and protoveratrine from Veratrum, reserpine 

 and recanescine from Rauwolfia, and the dimethoxy-furanochromones khellin 

 and visnagin from Khella. In pharmacy many of these constituents are dis- 

 pensed under trade names, for example, Veriloid and Veralba for Veratrum, 

 Raudixin for Rauwolfia root, Serpasil, Sandril, and Reserpoid for Rauwolfia 

 alkaloids, Eskel, Visnico, and Ammiven representing Khella components; and 

 there are several others. The large number of such products reflect the ex- 

 tensive commercial development of these once "obsolete" drugs. 



The question naturally raised is what differences do Veratrum, Rauwolfia, 

 and khellin pcssess with each other and over other well-established vasodi- 

 lators in the treatment of essential hypertension? Veratrum and its alkaloids 

 cause widespread reflex vasodilatation, including that of cerebral and renal 

 arteries, and its effects are more rapid than the other two botanical agents. 

 However, much evidence can be shown that Veratrum- alkaloids or crude 

 drugs are not significantly effective by the oral route in the majority of 

 ambulatory hypertensive patients, and rather high incidences of toxicity have 

 been reported following their use, i.e., vomiting and hiccoughing. Much better 

 results have been reported from the use of the alkaloids via the parenteral 

 route. When combined with rauwolfia and hexamethonium compounds these 



