Co-operative Clinical Trial of Alpha-methyldopa
Authors: WILLIAM M. SMITH
Journal: Annals of Internal Medicine (1966)

Article1 October 1966Co-operative Clinical Trial of Alpha-methyldopaIII. Double-blind Control Comparison of Alpha-methyldopa and Chlorothiazide, and Chlorothiazide and RauwolfiaWILLIAM M. SMITH, M.D., F.A.C.P., BRUCE BACHMAN, M.D., JAMES G. GALANTE, M.D., ERNEST G. HANOWELL, M.D., F.A.C.P., WILLARD P. JOHNSON, M.D., CHARLES E. KOCH JR., M.D., STANLEY D. KORFMACHER, M.D., RICHARD H. THURM, M.D., F.A.C.P., LOUIS BROMER, B.A.WILLIAM M. SMITH, M.D., F.A.C.P., BRUCE BACHMAN, M.D., JAMES G. GALANTE, M.D., ERNEST G. HANOWELL, M.D., F.A.C.P., WILLARD P. JOHNSON, M.D., CHARLES E. KOCH JR., M.D., STANLEY D. KORFMACHER, M.D., RICHARD H. THURM, M.D., F.A.C.P., LOUIS BROMER, B.A.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-65-4-657 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlpha-methyldopa (alpha-methyl-3,4-dihydroxy-L-phenylalanine) has been shown to inhibit the decarboxylation of aromatic L-amino acids and to deplete tissue stores of norepinephrine. The studies of Sjoerdsma, Vendsalu, and Engelman (1) have shown that these two properties are clearly dissociable. Available evidence indicates that the hypotensive action of alpha-methyldopa is not via decarboxylation inhibition but rather is mediated by amine metabolites of the compound itself, such as alpha-methyldopamine and alpha-methylnorepinephrine. These are formed after its decarboxylation and may function as "false transmitters," competing with norepinephrine for storage sites, from which they may be poorly released or less effective or both (2). Numerous investigators...References1. SJOERDSMAVENDSALUENGELMAN AAK: Studies on metabolism and mechanism of action of methyldopa. Circulation 28: 492, 1963. CrossrefMedlineGoogle Scholar2. WURTMAN RJ: Medical progress. Catecholamines. New Eng. J. Med. 273: 746, 1965. CrossrefMedlineGoogle Scholar3. GILLESPIEOATESCROUTSJOERDSMA LJAJRA: Clinical and chemical studies with α-methyl-dopa in patients with hypertension. Circulation 25: 281, 1962. CrossrefMedlineGoogle Scholar4. IRVINEO'BRIENNORTH ROKPJD: Alpha methyl dopa in treatment of hypertension. Lancet 1: 300, 1962. CrossrefGoogle Scholar5. DOLLERYHARRINGTON CTM: Methyl-dopa in hypertension—clinical and pharmacological studies. Ibid., p. 759. Google Scholar6. BAYLISSHARVEY-SMITH RIEA: Methyldopa in the treatment of hypertension. Ibid., p. 763. Google Scholar7. WEILBARBOURCHESNE MHBHRB: Alpha-methyl dopa for the treatment of hypertension: clinical and pharmacodynamic studies. Circulation 28: 165, 1963. CrossrefMedlineGoogle Scholar8. WILSONOKUNTETREAULT WRRL: Methyldopa and hydrochlorothiazide in primary hypertension: controlled clinical trial of drugs singly and in combination. JAMA 185: 819, 1963. CrossrefMedlineGoogle Scholar9. IGLOE MC: Effects of methyldopa in hypertension. JAMA 189: 188, 1964. CrossrefMedlineGoogle Scholar10. COLWILLDUTTONMORRISSEYYU JMAMJRN: Alpha-methyldopa and hydrochlorothiazide. A controlled study of their comparative effectiveness as antihypertensive agents. New Eng. J. Med. 271: 696, 1964. CrossrefMedlineGoogle Scholar11. OATESSELIGMANNCLARKROUSSEAULEE JAAWMAPRE: The relative efficacy of guanethidine, methyl dopa and pargyline as antihypertensive agents. New Eng. J. Med. 273: 729, 1965. CrossrefMedlineGoogle Scholar12. OATESGILLESPIEUDENFRIENDSJOERDSMA JALSA: Decarboxylase inhibition and blood pressure reduction by α-methyl-3, 4-dihydroxy-DL phenylanine. Science 131: 1890, 1960. CrossrefMedlineGoogle Scholar13. LEONARDGIFFORDHUMPHREY JWRWDC: Febrile reactions to L-alpha-methyl-dopa. Report of three cases. Cleveland Clin. Quart. 29: 144, 1962. Google Scholar14. SHEPSSCHIRGEROSMUNDSONFAIRBAIRN SGAPJJF: Methyldopa for treatment of hypertension. JAMA 184: 616, 1963. CrossrefMedlineGoogle Scholar15. SMITHDAMATOGALLUZZIGARFIELDHANOWELLSTIMSONTHURMWALSHBROMER WMANNJCFEGWHRHJJL: The evaluation of antihypertensive therapy: cooperative clinical trial method: I. Double-blind control comparison of chlorothiazide, rauwolfia serpentina, and hydralazine. Ann. Intern. Med. 61: 829, 1964. LinkGoogle Scholar16. U. S. Public Health Service Cooperative Study: Evaluation of antihypertensive therapy. II. Double-blind controlled evaluation of mebutamate. JAMA 193: 727, 1965. CrossrefMedlineGoogle Scholar17. FEDERER WT: Experimental design. Macmillan Co., New York, 1955, Chapt. II, IV. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: WILLIAM M. SMITH, M.D., F.A.C.P.; BRUCE BACHMAN, M.D.; JAMES G. GALANTE, M.D.; ERNEST G. HANOWELL, M.D., F.A.C.P.; WILLARD P. JOHNSON, M.D.; CHARLES E. KOCHJR., M.D.; STANLEY D. KORFMACHER, M.D.; RICHARD H. THURM, M.D., F.A.C.P.; LOUIS BROMER, B.A.Affiliations: San Francisco, CaliforniaFrom the U. S. Public Health Service, Division of Hospitals: Baltimore, Md., Boston, Mass., New Orleans, La., Norfolk, Va., San Francisco, Calif., Seattle, Wash., and Staten Island, N. Y.This investigation was supported in part by research grants HE-05311 and HE-08217, National Institutes of Health, Bethesda, Md.Requests for reprints should be addressed to William M. Smith, M.D., U. S. Public Health Service Hospital, 15th Ave. and Lake St., San Francisco, Calif. 94118. 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