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. 1967 May;106(5):388–399.

Recent Concepts in the Clinical Pharmacology of Anithypertensive Drugs

Alan S Nies, Kenneth L Melmon
PMCID: PMC1502719  PMID: 18730059

Abstract

As yet, no perfect drug has been found which can reduce supine and standing blood pressure equally, alter primarily peripheral vascular resistance, increase flow to the kidneys and be free of untoward effects. The thiazides, which act directly on the vessels and α methyl dopa, which causes an incomplete sympathetic blockade, are the two agents which come closest to the ideal. The advances which have resulted from the discovery of the false neurotransmitters may be expected to lead to the discovery of non-toxic drugs which cause subtle changes in the nerve ending and more controlled sympathetic blockade.

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Selected References

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  1. BREST A. N., ONESTI G., HEIDER C., MOYER J. H. Cardiac and renal hemodynamic response to pargyline. Ann N Y Acad Sci. 1963 Jul 8;107:1016–1022. doi: 10.1111/j.1749-6632.1963.tb13345.x. [DOI] [PubMed] [Google Scholar]
  2. BURN J. H., RAND M. J. ACETYLCHOLINE IN ADRENERGIC TRANSMISSION. Annu Rev Pharmacol. 1965;5:163–182. doi: 10.1146/annurev.pa.05.040165.001115. [DOI] [PubMed] [Google Scholar]
  3. CARLSSON A., LINDQVIST M. In-vivo decarboxylation of alpha-methyl DOPA and alpha-methyl metatyrosine. Acta Physiol Scand. 1962 Jan;54:87–94. doi: 10.1111/j.1748-1716.1962.tb02331.x. [DOI] [PubMed] [Google Scholar]
  4. CHANG C. C., COSTA E., BRODIE B. B. INTERACTION OF GUANETHIDINE WITH ADRENERGIC NEURONS. J Pharmacol Exp Ther. 1965 Mar;147:303–312. [PubMed] [Google Scholar]
  5. Conradi E. C., Gaffney T. E., Fink D. A., Vangrow J. S. Reversal of sympathetic nerve blockade: a comparison of dopa, dopamine, and norepinephrine with their alpha-methylated analogues. J Pharmacol Exp Ther. 1965 Oct;150(1):26–33. [PubMed] [Google Scholar]
  6. DAY M. D., RAND M. J. Evidence for a competitive antagonism of guanethidine by dexamphetamine. Br J Pharmacol Chemother. 1963 Feb;20:17–28. doi: 10.1111/j.1476-5381.1963.tb01293.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DAY M. D., RAND M. J. SOME OBSERVATIONS ON THE PHARMACOLOGY OF ALPHA-METHYLDOPA. Br J Pharmacol Chemother. 1964 Feb;22:72–86. doi: 10.1111/j.1476-5381.1964.tb01545.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DEWAR H. A., PEASTON M. J. THREE CASES RESEMBLING POLYARTERITIS NODOSA ARISING DURING TREATMENT WITH GUANETHIDINE. Br Med J. 1964 Sep 5;2(5409):609–611. doi: 10.1136/bmj.2.5409.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dollery C. T. Methyldopa in the treatment of hypertension. Prog Cardiovasc Dis. 1965 Nov;8(3):278–289. doi: 10.1016/s0033-0620(65)80019-6. [DOI] [PubMed] [Google Scholar]
  10. FISCHER J. E., HORST W. D., KOPIN I. J. BETA-HYDROXYLATED SYMPATHOMIMETIC AMINES AS FALSE NEUROTRANSMITTERS. Br J Pharmacol Chemother. 1965 Apr;24:477–484. doi: 10.1111/j.1476-5381.1965.tb01737.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FLETCHER G. F. Hypotensive reactions after small doses of reserpine given parenterally. N Engl J Med. 1963 Feb 7;268:309–310. doi: 10.1056/NEJM196302072680610. [DOI] [PubMed] [Google Scholar]
  12. FREIS E. D. Antihypertensive agents. I. N Engl J Med. 1962 Mar 8;266:507–509. doi: 10.1056/nejm196203082661010. [DOI] [PubMed] [Google Scholar]
  13. Fischer J. E., Weise V. K., Kopin I. J. Release of tritiated bretylium by sympathetic nerve stimulation. Nature. 1966 Feb 19;209(5025):778–779. doi: 10.1038/209778a0. [DOI] [PubMed] [Google Scholar]
  14. Freis E. D. Guanethidine. Prog Cardiovasc Dis. 1965 Sep;8(2):183–193. doi: 10.1016/s0033-0620(65)80008-1. [DOI] [PubMed] [Google Scholar]
  15. HORWITZ D., SJOERDSMA A. EFFECTS OF ALPHA-METHYL-META-TYROSINE INTRAVENOUSLY IN MAN. Life Sci. 1964 Jan;3:41–48. doi: 10.1016/0024-3205(64)90224-3. [DOI] [PubMed] [Google Scholar]
  16. Haefely W., Hürlimann A., Thoenen H. The effect of stimulation of sympathetic nerves in the cat treated with reserpine, alpha-methyldopa and alpha-methylmetatyrosine. Br J Pharmacol Chemother. 1966 Jan;26(1):172–185. doi: 10.1111/j.1476-5381.1966.tb01819.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hollander W., Wilkins R. W. The pharmacology and clinical use of rauwolfia, hydralazine, thiazides, and aldosterone antagonists in arterial hypertension. Prog Cardiovasc Dis. 1966 Jan;8(4):291–318. doi: 10.1016/s0033-0620(66)80008-7. [DOI] [PubMed] [Google Scholar]
  18. KOPIN I. J., FISCHER J. E., MUSACCHIO J. M., HORST W. D., WEISE V. K. "FALSE NEUROCHEMICAL TRANSMITTERS" AND THE MECHANISM OF SYMPATHETIC BLOCKADE BY MONOAMINE OXIDASE INHIBITORS. J Pharmacol Exp Ther. 1965 Feb;147:186–193. [PubMed] [Google Scholar]
  19. LEISHMAN A. W., MATTHEWS H. L., SMITH A. J. Anatgonism of guanethidine by imipramine. Lancet. 1963 Jan 12;1(7272):112–112. doi: 10.1016/s0140-6736(63)91123-1. [DOI] [PubMed] [Google Scholar]
  20. LEISHMAN A. W., SANDLER G. HASTENING THE CONTROL OF BLOOD-PRESSURE BY GUANETHIDINE. Lancet. 1965 Mar 27;1(7387):668–670. doi: 10.1016/s0140-6736(65)91825-8. [DOI] [PubMed] [Google Scholar]
  21. LEONARD J. W., GIFFORD R. W., Jr, HUMPHREY D. C. TREATMENT OF HYPERTENSION WITH METHYLDOPA ALONE OR COMBINED WITH DIURETICS AND OR GUANETHIDINE. A REPORT OF 63 CASES. Am Heart J. 1965 May;69:610–618. doi: 10.1016/0002-8703(65)90242-5. [DOI] [PubMed] [Google Scholar]
  22. LEONBERG S. C., Jr, GREEN J. B., ELLIOTT F. A. THE RESPONSE OF STROKE PATIENTS TO VERY SMALL DOSES OF PARENTERAL RESERPINE. Ann Intern Med. 1964 May;60:866–870. doi: 10.7326/0003-4819-60-5-866. [DOI] [PubMed] [Google Scholar]
  23. LEVINE R. J., SJOERDSMA A. DISSOCIATION OF THE DECARBOXYLASE-INHIBITING AND NOREPINEPHRINE-DEPLETING EFFECTS OF ALPHA-METHYL-DOPA, ALPHA-ETHYL-DOPA, 4-BROMO-3-HYDROXY-BENZYLOXYAMINE AND RELATED SUBSTANCES. J Pharmacol Exp Ther. 1964 Oct;146:42–47. [PubMed] [Google Scholar]
  24. LUKE R. G., KENNEDY A. C. METHYLDOPA IN TREATMENT OF HYPERTENSION DUE TO CHRONIC RENAL DISEASE. Br Med J. 1964 Jan 4;1(5374):27–30. [PMC free article] [PubMed] [Google Scholar]
  25. Levine R. J., Strauch B. S. Hypertensive responses to methyldopa. N Engl J Med. 1966 Oct 27;275(17):946–948. doi: 10.1056/NEJM196610272751708. [DOI] [PubMed] [Google Scholar]
  26. MASON D. T., BRAUNWALD E. EFFECTS OF GUANETHIDINE, RESERPINE, AND METHYLDOPA ON REFLEX VENOUS AND ARTERIAL CONSTRICTION IN MAN. J Clin Invest. 1964 Jul;43:1449–1463. doi: 10.1172/JCI105021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. MORIN Y., TURMEL L., FORTIER J. METHYLDOPA: CLINICAL STUDIES IN ARTERIAL HYPERTENSION. Am J Med Sci. 1964 Dec;248:633–639. [PubMed] [Google Scholar]
  28. MUSCHOLL E., MAITRE L. RELEASE BY SYMPATHETIC STIMULATION OF ALPHA-METHYLNORADRENALINE STORED IN THE HEART AFTER ADMINISTRATION OF ALPHA-METHYLDOPA. Experientia. 1963 Dec 15;19:658–659. doi: 10.1007/BF02151307. [DOI] [PubMed] [Google Scholar]
  29. Musacchio J. M., Fischer J. E., Kopin I. J. Subcellular distribution and release by sympathetic nerve stimulation of dopamine and alpha-methyl dopamine. J Pharmacol Exp Ther. 1966 Apr;152(1):51–55. [PubMed] [Google Scholar]
  30. Musacchio J. M., Goldstein M., Anagnoste B., Poch G., Kopin I. J. Inhibition of dopamine-beta-hydroxylase by disulfiram in vivo. J Pharmacol Exp Ther. 1966 Apr;152(1):56–61. [PubMed] [Google Scholar]
  31. NAGATSU T., LEVITT M., UDENFRIEND S. TYROSINE HYDROXYLASE. THE INITIAL STEP IN NOREPINEPHRINE BIOSYNTHESIS. J Biol Chem. 1964 Sep;239:2910–2917. [PubMed] [Google Scholar]
  32. NUESSLE W. F., NORMAN F. C., MILLER H. E. PICKLED HERRING AND TRANYLCYPROMINE REACTION. JAMA. 1965 May 24;192:726–727. doi: 10.1001/jama.1965.03080210070029. [DOI] [PubMed] [Google Scholar]
  33. OATES J. A., DOCTOR R. B. ANTIHYPERTENSIVE AGENTS WHICH IMPAIR ADRENERGIC NEURON TRANSMISSION. Postgrad Med. 1965 Jan;37:58–64. doi: 10.1080/00325481.1965.11695398. [DOI] [PubMed] [Google Scholar]
  34. OATES J. A., GILLESPIE L., UDENFRIEND S., SJOERDSMA A. Decarboxylase inhibition and blood pressure reduction by alpha-methyl-3,4-dihydroxy-DL-phenylalanine. Science. 1960 Jun 24;131(3417):1890–1891. doi: 10.1126/science.131.3417.1890. [DOI] [PubMed] [Google Scholar]
  35. ORVIS H. H., TAMAGNA I. G., HORWITZ D., THOMAS R. Correlation of hypotensive effects and urinary tryptamine levels during pargyline therapy. Ann N Y Acad Sci. 1963 Jul 8;107:958–965. doi: 10.1111/j.1749-6632.1963.tb13339.x. [DOI] [PubMed] [Google Scholar]
  36. Oates J. A., Seligmann A. W., Clark M. A., Rousseau P., Lee R. E. The relative efficacy of guanethidine, methyldopa and pargyline as antihypertensive agents. N Engl J Med. 1965 Sep 30;273(14):729–734. doi: 10.1056/NEJM196509302731402. [DOI] [PubMed] [Google Scholar]
  37. PARKS V. J., SANDISON A. G., SKINNER S. L., WHELAN R. F. The mechanism of the vasodilator action of reserpine in man. Clin Sci. 1961 Jun;20:289–295. [PubMed] [Google Scholar]
  38. PETTINGER W. A., HORWITZ D., SJOERDSMA A. Lactation due to methyldopa. Br Med J. 1963 Jun 1;1(5343):1460–1460. doi: 10.1136/bmj.1.5343.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Peart W. S. Cathecholamines and hypertension. Pharmacol Rev. 1966 Mar;18(1):667–672. [PubMed] [Google Scholar]
  40. SHORE P. A., BUSFIELD D., ALPERS H. S. BINDING AND RELEASE OF METARAMINOL: MECHANISM OF NOREPINEPHRINE DEPLETION BY ALPHA-METHYL-M-TYROSINE AND RELATED AGENTS. J Pharmacol Exp Ther. 1964 Nov;146:194–199. [PubMed] [Google Scholar]
  41. SJOERDSMA A., VENDSALU A., ENGELMAN K. STUDIES ON THE METABOLISM AND MECHANISM OF ACTION OF METHYLDOPA. Circulation. 1963 Oct;28:492–502. doi: 10.1161/01.cir.28.4.492. [DOI] [PubMed] [Google Scholar]
  42. SMITH W. M., DAMATO A. N., GALLUZZI N. J., GARFIELD C. F., HANOWELL E. G., STIMSON W. H., THURM R. H., WALSH J. J., BROMER L. THE EVALUATION OF ANTIHYPERTENSIVE THERAPY COOPERATIVE CLINICAL TRIAL METHOD. I. DOUBLE-BLIND CONTROL COMPARISON OF CHLOROTHIAZIDE, RAUWOLFIA SERPENTINA, AND HYDRALAZINE. Ann Intern Med. 1964 Nov;61:829–846. [PubMed] [Google Scholar]
  43. Smith W. M., Bachman B., Galante J. G., Hanowell E. G., Johnson W. P., Koch C. E., Jr, Korfmacher S. D., Thurm R. H., Bromer L. Co-operative clinical trial of alpha-methyldopa. 3. Double-blind control comparison of alpha-methyldopa and chlorothiazide, and chlorothiazide and rauwolfia. Ann Intern Med. 1966 Oct;65(4):657–671. doi: 10.7326/0003-4819-65-4-657. [DOI] [PubMed] [Google Scholar]
  44. Sokolow M., Perloff D. The choice of drugs and the management of essential hypertension. Prog Cardiovasc Dis. 1965 Nov;8(3):253–277. doi: 10.1016/s0033-0620(65)80018-4. [DOI] [PubMed] [Google Scholar]
  45. Stone C. A., Porter C. C. Methyldopa and adrenergic nerve function. Pharmacol Rev. 1966 Mar;18(1):569–575. [PubMed] [Google Scholar]
  46. Udenfriend S. Tyrosine hydroxylase. Pharmacol Rev. 1966 Mar;18(1):43–51. [PubMed] [Google Scholar]
  47. Waal H. J. Hypotensive action of propranolol. Clin Pharmacol Ther. 1966 Sep-Oct;7(5):588–598. doi: 10.1002/cpt196675588. [DOI] [PubMed] [Google Scholar]
  48. Wurtman R. J. Catecholamines. N Engl J Med. 1965 Sep 23;273(13):693–contd. doi: 10.1056/NEJM196509232731306. [DOI] [PubMed] [Google Scholar]

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