Co-operative Clinical Trial of Alpha-methyldopa

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. 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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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