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American hellebore (Veratrum viride)


Veratrum viride
Synonyms / Common Names / Related Terms
Alkavevir, American false hellebore, American white hellebore, cevadine, corn lily, cryptenamine, cyclopamine, false hellebore, germidine, germitrine, green corn lily, green false hellebore, green hellebore, green veratrum, hellebore, Indian poke, itch weed, jervine, jervine alkaloids, Liliaceae (family), Melanthiaceae (subfamily), muldamine, O-acetyljervine, protoveratrine, poison lily, proveratrine, swamp hellebore, verat-v., veratramine, veratridine, Veratrum viride, Veratrone®, Veriloid®, Vergitryl®, Vertavis®, white American hellebore.

Note: Much of the toxicological data in this monograph is based on the European white hellebore (Veratrum album), as both American hellebore and European white hellebore contain jervine alkaloids, the constituents responsible for the plants' toxic cardiovascular effects.

Mechanism of Action

Pharmacology:

  • Constituents: There are more than 50 steroidal alkaloids found in American hellebore. Isolated chemical constituents include: O-acetyljervine, cevadine, cryptenamine, cyclopamine (11-deoxojervine), cycloposine, germitrine, germidine, jervine, muldamine, protoveratrine (A&B), veratramine, veratridine, and veriloid.8,4,9,10
  • Cardiovascular effects: American hellebore was studied during the late 1940s and early 1950s as a hypotensive agent in essential hypertension, hypertension during renal dysfunction, and eclampsic toxemia during pregnancy.11,4,1,12,5 In laboratory studies, the isolated steroidal compounds from American hellebore have been reported to significantly influence arterial pressure responses, decrease mean aortic pressure, cause renal, femoral and mesenteric vasodilation, and decrease the heart rate.13,10,14 American hellebore alkaloids do not seem to significantly affect cardiac output, suggesting diminished arteriolar resistance.3 The isolated constituent O-acetyljervine has been reported to have beta-agonist activity in laboratory studies.6
  • Several reports suggest that both oral and parenteral use of the isolated alkaloids found in American hellebore cause a fall in mean arterial pressure without a reduction in cardiac output.3,1 Early reports suggested the alkaloids cause vasodilation, and it was later found that an isolated alkaloid also had beta-adrenergic blocking activity.4,7 It was found that atropine abolishes the bradycardia induced by the isolated alkaloids of American hellebore but only partially reverses the hypotensive effects.3 No postural hypotension was noted with the administration of the isolated alkaloids.4,2
  • Renal effects: Mixed alkaloids from Veratrum species have been reported decrease glomerular filtration rate and effective renal blood flow. The isolated constituent protoveratrine has been reported to induce renal vasodilation at the glomerular aterioles in patients with chronic glomerulonephritis.1

Pharmacodynamics/Kinetics:

  • Insufficient available evidence.

References
  1. Meilman, E. and Krayer, O. Clinical studies on veratrum alkaloids; the action of protoveratrine and veratridine in hypertension. Circulation 1950;1(2):204-213. 15409589
  2. Assali, N. S., Brust, A. A., Garber, S. T., and Ferris, E. B. Comparative study of the effects of tetraethyl-ammonium chloride and veratrum viride on blood pressure in normal and toxemic pregnancy. J Clin Invest 1950;29(3):290-296. 16695799
  3. Freis, E. D., Stanton, J. R., Culbertson, J. W., Litter, J., Halperin, M. H., Burnett, C. H., and Wilkins, R. W. The hemodynamic effects of hypotensive drugs in man. i. veratrum viride. J Clin Invest 1949;28(2):353-368. 16695685
  4. Freis, E. D., Stanton, J. R., and MOISTER, F. C. Assay in man of the chemical fractions of Veratrum Viride, and identification of the pure alkaloids germitrine and germidine as potent hypotensive principles derived from the drug. J Pharmacol Exp Ther 1950;98(2):166-173. 15422510
  5. Stearns, N. S. and Ellis, L. B. Acute effects of intravenous administration of a preparation of Veratrum viride in patients with severe forms of hypertensive disease. N Engl J Med 3-13-1952;246(11):397-400. 14910826
  6. Gilani, AH, Aftab, K, Saeed, SA, and et al. O-Acetyljervine: new \b/-adrenoceptor agonist from Veratrum. Archives of Pharmacal Research (Korea) 1995;18:129-132.
  7. Prince, L. A. and Stork, C. M. Prolonged cardiotoxicity from poison lilly (Veratrum viride). Vet Hum Toxicol  2000;42(5):282-285. 11003119
  8. Chen, K. K., Henderson, F. G., and Anderson, R. C. The cardiac action of Helleborus glycosides and their aglycones. J Pharmacol Exp Ther 1950;99(4:1):325-400. 15437315
  9. Marchetti, G. [Effect of two new alkaloids of Veratrum viride on the circulatory apparatus.]. Arch Ital Sci Farmacol  1954;4(1):15-27. 13159580
  10. Roesch, E. [Effect of cevadine, veratridine and Veratrum viride extract on blood pressure and respiration in dog.]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol  1954;222(1-2):209-212. 13176492
  11. Barrow, J. G. and Sikes, C. R. The use of purified veratrum viride alkaloids in the treatment of essential hypertension. Am Heart J 1951;41(5):742-748. 14829406
  12. Shapiro, A. P. and Ferris, E. B. The effects of intravenously administered Veratrum viride in hypertensive and normotensive subjects. Ann Intern Med 1952;36(3):792-806. 14903783
  13. Korol, B., Zuber, A. V., and Miller, L. D. Carotid sinus pressure reflex bioassay for Veratrum viride. J Pharm Sci 1970;59(8):1110-1113. 5457326
  14. Zupko, A. G. and Edwards, L. D. A study of a depressor principle of Veratrum viride. J Am Pharm Assoc Am Pharm Assoc 1950;39(11):610-615. 14794527




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