RSS Feeds
Co-operative Clinical Trial of Alpha-methyldopa
III. Double-blind Control Comparison of Alpha-methyldopa and Chlorothiazide, and Chlorothiazide and Rauwolfia
- 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.; and
- LOUIS BROMER, B.A.
- 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.
Excerpt
Alpha-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
Acknowledgments
The support and participation of the following Associate Investigators are acknowledged: Anthony N. Damato, M.D., William B. Furgerson, Jr., M.D., Robert J. Griep, M.D., Claude R. Garfield, M.D., and Christfried J. Urner, M.D.
The invaluable help of the research assistants is likewise acknowledged. All drugs used in this investigation were supplied through the courtesy of E. L. Foltz, M.D., of Merck Sharp & Dohme Research Laboratories, West Point, Pa.
Summario in Interlingua
Cento octanta-novem subjectos con leve o moderate grados de hypertension completava cursos de tractamento de inter tres e octo menses in un studio del efficacia e toxicitate relative de dopa alpha-methylic. Iste agente sol esseva comparate con su combination con chlorothiazida e con chlorothiazida in combination con rauwolfia. Le sub-gruppamento del patientes esseva effectuate aleatorimente, e le piano de therapia utilisava le principio del duple anonymato. Le sub-gruppos de patientes esseva uniforme in numeros e in composition.
Significative declinos del tension occurreva in omne le sub-gruppos tanto in decubito dorsal como etiam in postura erecte. Le combination de chlorothiazida e rauwolfia esseva le medication le plus efficace, resultante in un declino del tension medie de 22,5 mm de Hg e in un satisfacente responsa general in 79 pro cento del casos. Le differentia inter iste e le altere modalitates es statisticamente significative. In subjectos in qui le tension medie de controlo habeva essite alte, le differentia inter le combination de chlorothiazida son rauwolfia e le combination de chlorothiazida con dopa alpha-methylic non pareva esser significative.
Effectos secundari de toxicitate non compromitteva seriemente le efficacia de ulle del modalitates. Somnolentia, lethargia, e siccitate buccal esseva le effectos secundari le plus commun de dopa alpha-methylic. Usualmente illos re-occurreva transientemente post omne augmento del dosage. Un apparente hepatotoxicitate esseva notate sed representava un problema minor e non poteva esser relationate specificamente con dopa alpha-methylic.
Article and Author Information
-
From 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.
-
- Received May 31, 1966.
- Accepted June 1, 1966.
Related Clinical Content
