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α-Adrenoceptor Antagonists

  • P. A. van Zwieten
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 93 / 1)

Abstract

Ever since the development of α-adrenoceptor antagonistic drugs (α-blockers), attempts have been made to treat arterial hypertensive disease with such compounds. This approach would seem logical since α-adrenoceptor antagonists are vasodilators with a very strong action in the arteriolar vascular bed; in addition it should be realized that elevated total peripheral resistance is the most consistent hemodynamic change in established essential hypertension. Treatment with vasodilator drugs thus seems a rational route to lower blood pressure in hypertensive patients.

Keywords

Total Peripheral Resistance Hypertensive Disease Hemodynamic Profile Reflex Tachycardia Precapillary Arteriole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Amery A (ed) (1986) Treatment of hypertension with urapidil. Preclinical and clinical update. R Soc Med Serv 101: 1–186Google Scholar
  2. Amann FW, Bolli P, Kiowski W et al. (1981) Enhanced α-adrenoceptor-mediated vasoconstriction in essential hypertension. Hypertension 3 (Suppl I): 119–123Google Scholar
  3. Awan N, Hermanovich J, Vera Z et al. (1982) Cardiocirculatory actions of trimazosin and sodium nitroprusside in ischemic heart disease. Clin Pharmacol Ther 31: 290PubMedCrossRefGoogle Scholar
  4. Bateman DN, Hobbs DC, Twomey TM et al. (1979) Prazosin, pharmacokinetics and concentration effect. Eur J Clin Pharmacol 16: 177–181PubMedCrossRefGoogle Scholar
  5. Berthelsen S, Pettinger WA (1977) A functional basis for classification of α-adrenergic receptors. Life Sci 21: 595–606PubMedCrossRefGoogle Scholar
  6. Brodde OE, Daul AE, O’Hara N, Bock KD (1984) Increased density and responsiveness of α- and p-adrenoceptors in circulating blood cells of essential hypertensive patients. J Hypertens 2 (Suppl 3): 111–113Google Scholar
  7. Brodde OE, Daul AE, O’Hara H, Khalifa AM (1985) Properties of α- and β-adrenoceptors in circulating blood cells of patients with essential hypertension. J Cardiovasc Pharmacol 7: S162–S167PubMedCrossRefGoogle Scholar
  8. Brogden RN, Heel RC, Speight TM, Avery GS (1977) Prazosin: a review of its pharmacological properties and therapeutic efficacy in hypertension. Drugs 14: 163–197PubMedCrossRefGoogle Scholar
  9. Buehler FR, Bolli P, Erne P, Kiowski W, Mueller FB, Hulth6n UL, Ji BH (1985) Adrenoceptors, calcium and vasoconstriction in normal and hypertensive humans. J Cardiovasc Pharmacol 7. S130–S136CrossRefGoogle Scholar
  10. Cambridge D, Davey MJ, Massingham R (1977) The pharmacology of antihypertensive drugs with special reference to vasodilators, α-adrenergic blocking agents and prazosin. Med J Aust (Suppl 2 ): 2Google Scholar
  11. Cambridge D, Davey MJ, Greengrass PM (1980) The pharmacology of antihypertensive drugs with special reference to vasodilators, α-adrenergic blocking agents and prazosin. Prog Pharmacol 3: 107Google Scholar
  12. Cavero I (1982) Effects of prazosin on reflex changes in heart rate evoked by vasopressor and vasodepressor stimuli in conscious rabbits. J Cardiovasc Pharmacol 4 (Suppl): S108PubMedCrossRefGoogle Scholar
  13. Cavero I, Roach AG (1980) The pharmacology of prazosin, a novel antihypertensive agent. Life Sci 27: 1525–1533PubMedCrossRefGoogle Scholar
  14. Constantine JW, Hess HJ (1981) The cardiovascula effects of trimazosin. Eur J Pharmacol 74: 227PubMedCrossRefGoogle Scholar
  15. Constantine JW, McShane WK, Scriabine A, Hess HJ (1973) Analysis of the hypotensive action of prazosin. In: Onesti G, Kim KE, Moyer JH (eds) Hypertension: mechanisms and management. Grune and Stratton, New York, p 429Google Scholar
  16. Constantine JW, Weeks RA, McShane WK (1978) Prazosin and presynaptic α-receptors in the cardio-accelerator nerve of the dog. Eur J Pharmacol 50: 51PubMedCrossRefGoogle Scholar
  17. Cubeddu LX, Zarate NA, Rosales CB, Zschaek W (1982) Prazosin and propranolol in preoperative management of phaeochromocytoma. Clin Pharmacol Ther 32: 156–160PubMedCrossRefGoogle Scholar
  18. De Jonge A, Timmermans PBMWM, Van Zwieten PA (1981) Participation of cardiac presynaptic α2-adrenoceptors in the bradycardiac effects of Clonidine and analogues. Nauyn Schmiedebergs Arch Pharmacol 317: 8–12CrossRefGoogle Scholar
  19. Doxey JC, Smith CFC, Walker JM (1977) Selectivity of blocking agents for pre- and postsynaptic α-adrenoceptors. Br J Pharmacol 60: 91PubMedGoogle Scholar
  20. Drayer JIM, Weber MA, De Young JL, Brewer DD (1983) Long term blood pressure monitoring in the evaluation of antihypertensive therapy. Arch Intern Med 143: 898–901PubMedCrossRefGoogle Scholar
  21. Elliott HL, McLean K, Sumner DJ et al. (1981) Immediate cardiovascular responses to oral prazosin—effects on current β-blockers. Clin Pharmacol Ther 29: 303PubMedCrossRefGoogle Scholar
  22. Elliott HL, Meredith PA, Sumner DJ et al. (1982) A pharmacodynamic and pharmacokinetic assessment of a new a-adrenoceptor antagonist, doxazosin (UK 33274) in normotensive subjects. Br J Clin Pharmacol 13: 699PubMedGoogle Scholar
  23. Georgopoulos AJ, Valasidis A, Siourthas D (1978) Treatment of chronic heart failure with slow release phentolamine. Eur J Clin Pharmacol 13: 325PubMedCrossRefGoogle Scholar
  24. Gould L, Becker WH, Macklin EE (1980) Effects of intravenous phentolamine on hemodynamics and restind pulmonary gas exchange in man. Angiology 31: 120PubMedCrossRefGoogle Scholar
  25. Graham RM, Pettinger WA (1979) Prazosin. N Engl J Med 300: 232–236CrossRefGoogle Scholar
  26. Greengrass PM, Bremner R (1979) Binding characteristics of 3H-prazosin to rat brain α-adrenergic receptors. Eur J Pharmacol 55: 323PubMedCrossRefGoogle Scholar
  27. Hamilton CA, Reid JL, Vincent J (1985) Pharmacokinetic and pharmacodynamic studies with two α-adrenoceptor antagonists, doxazosin and prazosin in the rabbit. Br J Pharmacol 86: 79–87PubMedGoogle Scholar
  28. Hardey DW, Lokhandwala MF (1979) Influence of prazosin on cardiac reflex function. Eur J Pharmacol 57: 251PubMedCrossRefGoogle Scholar
  29. Hess HJ (1974) Biochemistry and structure-activity studies with prazosin. In: Cotton DKW (ed) Prazosin—evaluation of a new antihypertensive agent. Excerpta Medica, Amsterdam, p 5Google Scholar
  30. Hornung R, Presek P, Glossman H (1979) Alpha-adrenoceptors in rat brain: direct identification with prazosin. Naunyn Schmiedebergs Arch. Pharmacol 308: 223Google Scholar
  31. Huchet AM, Velly J, Schmitt H (1981) Role of αr and α2-adrenoceptors in the modulation of the baroreflex vagal bradycardia. Eur J Pharmacol 71: 455–461PubMedCrossRefGoogle Scholar
  32. Imhof PR, Carnier B, Brunner L, Keller G, Rohrer T (1976) Human Pharmacology of orally administered phentolamine. In: Taylor SH (ed) Phentolamine in heart failure and other cardiac disorders. Huber, Bern, pp 11–22Google Scholar
  33. Jie K, Van Brummelen P, Vermey P, Timmermans PBMWM, Van Zwieten PA (1984) Identification of vascular postsynaptic αr and α2-adrenoceptors in man. Circ Res 54: 447–452PubMedGoogle Scholar
  34. Jie K, Van Brummelen P, Vermey P, Timmermans PBMWM, Van Zwieten PA (1986) ar and α2-Adrenoceptor mediated vasoconstriction in the forearm of normotensive and hypertensive subjects. J Cardiovasc Pharmacol 8: 190–196Google Scholar
  35. Jones CR, Hamilton CA, Whyte KF, Elliott HL, Reid JL (1985) Acute and chronic α-Adrenoceptor regulation of alpha(2)-adrenoceptor number and function in man. Clin Sci 68 (Suppl 10): 129S–132SPubMedGoogle Scholar
  36. Kiowski W, Hulthen UL, Ritz R, Buehler FR (1983) Alpha-2-adrenoceptor mediated vasoconstriction in human arterial vessels. J Clin Pharmacol Ther 34: 565–569CrossRefGoogle Scholar
  37. Kobinger W (1978) Central a-adrenergic systems as targets for hypotensive drugs. Rev Physiol Biochem Pharmacol 81: 40–100Google Scholar
  38. Kobrin I, Gallo A, Kumar A, Pegram BL, Fröhlich ED (1984) Immediate hemodynamic changes produced by Urapidil in normotensive and spontaneously hypertensive rats. Clin Exp Hypertens A6: 685–697CrossRefGoogle Scholar
  39. Kondo K, Ohashi K, Ebiwara A (1982) Pharmacokinetics and pharmacological effects of terazosin, a new alpha-blocker. Jpn J Clin Pharmacol Ther 13: 137–138CrossRefGoogle Scholar
  40. Kyncl JJ (1986) The pharmacology of terazosin. Am J Med 80 (Suppl 5B): 12–19PubMedCrossRefGoogle Scholar
  41. Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32: 337–362Google Scholar
  42. Langer SZ, Massingham R, Shepperson NB (1980) Presence of postsynaptic α2-adrenoceptors of predominantly extrasynaptic location in the vascular smooth muslce of the dog hind limb. Clin Sci 59 (Suppl 6): 225S–228SPubMedGoogle Scholar
  43. Lefövre-Borg F, Roach AG, Gomeni R, Cavero I (1979) Mechanism of antihypertensive activity of orally administered prazosin in spontaneously hypertensive rats. J Cardiovasc Pharmacol 1: 31CrossRefGoogle Scholar
  44. Lund-Johansen P (1974) Hemodynamic changes at rest and during exercise in long-term prazosin therapy of essential hypertension. In: Cotton DKW (ed) Prazosin—evaluation of a new antihypertensive agent. Excerpta Medica, Amsterdam, p 43Google Scholar
  45. Lui HK, Awan NA, Needham K, Mason DT (1985) Comparative evaluation of the new oral systemic vasodilator terazosin and nitroprusside in severe chronic heart failure. Clin Res 33: 207AGoogle Scholar
  46. Marshall AJ, Kettle MA, Barritt DW (1980) Evaluation of indoramin added to Oxprenolol and bendrofluazide as a third agent in severe hypertension. Br J Clin Pharmacol 10: 217PubMedGoogle Scholar
  47. Messerli FH, Kobrin I, Amodeo C, Ventura HO, Fröhlich ED (1986) Immediate cardiovascular effects of Urapidil in essential hypertension. In: Amery A (ed) Treatment of hypertension with Urapidil. Roy Soc Med Serv 101: 87–91Google Scholar
  48. Miach PJ, Dausse JP, Cardot A, Meyer P (1980) 3H-Prazosin binds specifically to ar adrenoceptors in rat brain. Naunyn Schmiedebergs Arch Pharmacol 312: 23Google Scholar
  49. Moser M (ed) (1986) Advances in the management of hypertension: focus on terazosin, a new alpha-l-adrenergic antagonist. Am J Med 80 (5B): 1–105Google Scholar
  50. Motulsky HJ, O’Connor DT, Insel PA (1983) Platelet a2-adrenergic receptors in treated and untreated essential hypertension. Clin Sei 64: 265–272Google Scholar
  51. Perry RS (1985) Trimazosin. Drugs Today 21: 243–252Google Scholar
  52. Persson B, Yao T, Thoren P (1981) Correlation between decreased heart rate and central inhibition of sympathetic discharges after prazosin administration in the spontaneously hypertensive rat. Clin Exp Hypertens 3: 245–250PubMedCrossRefGoogle Scholar
  53. Philipp T, Distler A, Cordes U (1978) Sympathetic nervous system and blood pressure control in essential hypertension. Lancet 2: 959–963PubMedCrossRefGoogle Scholar
  54. Preston RA, O’Connor DT, Stone RA (1979) Prazosin and renal hemodynamics: arteriolar vasodilatation during therapy of essential hypertension in man. J Cardiovasc Pharmacol 1: 277PubMedCrossRefGoogle Scholar
  55. Ramage AG (1982) Why do aradrenoceptor antagonists fail to cause reflex tachycardia? Br J Pharmacol 77 (Suppl): 323 PGoogle Scholar
  56. Reid JL, Meredith PA, Elliott H (1983) Pharmacokinetics and pharmacodynamic of trimazosin in man. Am Heart J 106: 1222–1228PubMedCrossRefGoogle Scholar
  57. Roach AG, Gomeni R, Mitchard M et al. (1978) The blood pressure lowering effects of intravenous versus intracerebroventricular prazosin in anesthetized cats. Eur J Pharmacol 49: 271–274PubMedCrossRefGoogle Scholar
  58. Robinson BF (1981) Drugs acting directly on vascular smooth muscle: circulatory and secondary effects. Br J Pharmacol 12: 5SGoogle Scholar
  59. Roesler JM, McCafferty JP, De Marinis RM, Matthews WD, Hieble JP (1986) Characterization of the antihypertensive activity of SK & F 86466, a selective α2-antagonist in the rat. J Pharmacol Exp Ther 236: 1–7PubMedGoogle Scholar
  60. Saeed M, Sommer O, Holtz J, Bassenge E (1982) α-Adrenoceptor blockade by phentolamine causes β-adrenergic vasodilatation by increased catecholamine release due to presynaptic a-blockade. J Cardiovasc Pharmacol 4: 44–48Google Scholar
  61. Sands H, Jorgensen R (1979) Effects of prazosin on cyclic nucleotide content and blood pressure of the spontaneously hypertensive rat. Biochem Pharmacol 28: 685–687PubMedCrossRefGoogle Scholar
  62. Sasso EH, O’Conner DT (1982) Prazosin depression of baroreflex function in hypertensive man. Eur J Clin Pharmacol 22: 7–9PubMedCrossRefGoogle Scholar
  63. Schmitt H (1971) Action des a-sympathomimetiques sur les structures nerveuses. Actual Pharmacol 24: 93–113Google Scholar
  64. Schoetensack W, Bruckschen EG, Zech K (1983) Urapidil. In: Scriabine W (ed) New drugs annual: Cardiovascular drugs. Raven, New York, pp 19–48Google Scholar
  65. Singleton W, Saxton CAPD, Hernandez R, Ferrer RS, Pritchard BNC (1980) Alpha blocking effect of prazosin, trimazosin and UK-33,274 in man. In: Turner P (ed) World conference on clin pharmac ther Abs. MacMillan, LondonGoogle Scholar
  66. Singleton W, Sexton CAPD, Hernandez J, Prichard BN (1982). Postjunctional selectivity of α-blockade with prazosin, trimazosin and UK-33,274 in man. J Cardiovasc Pharmacol 4: S145–S155PubMedCrossRefGoogle Scholar
  67. Sonders RC (1986) The pharmacokinetics of terazosin. Am J Med 80: (Suppl 5B): 77–81CrossRefGoogle Scholar
  68. Stanaszek WF, Kellerman D, Brogden RN (1983) Romankiewicz. Prazosin update. A review of its pharmacological properties and therapeutic use in hypertension and congestive heart failure. Drugs 25: 339–384Google Scholar
  69. Starke K (1981) α-Adrenoceptor subclassification. Rev Physiol Biochem Pharmacol 88:199–236Google Scholar
  70. Stokes GS, Frost GW, Graham RM, MacCarthy EP (1979) Indoramin and prazosin as adjuncts to beta-adrenoceptor blockade in hypertension. Clin Pharmacol Ther 25: 783–785PubMedGoogle Scholar
  71. Taylor CR, Leader JP, Singleton MB, Munster EW, Falkner FC (1983) Profile of trimazosin: an effective and safe antihypertensive agent. Am Heart J 106: 1269–1285PubMedCrossRefGoogle Scholar
  72. Taylor LA, Twomey TM, Schuch von Wintenau M (1977) The metabolic fate of prazosin. Xenobiotica 7: 357–364Google Scholar
  73. Timmermans PBMWM, Van Zwieten PA (1981) The postsynaptic α2-adrenoceptor. J Auton Pharmacol 1: 171–183PubMedCrossRefGoogle Scholar
  74. Timmermans PBMWM, Van Zwieten PA (1982) α2-Adrenoceptors: classification, localisation, mechanisms and targets for drugs. J Med Chem 25: 1389–1401Google Scholar
  75. Timmermans PBMWM, Lam E, Van Zwieten PA (1979) The interaction between prazosin and Clonidine at α-adrenoceptors in rats and cats. Eur J Pharmacol 49: 271–276Google Scholar
  76. Timmermans PBMWM, Kwa HY, Karamat Ali F, Van Zwieten PA (1980) Prazosin and its analogues UK-18,596 and UK-33,274: a comparative study on cardiovascular effects and α-adrenoceptor blocking activities. Arch Int Pharmacodyn 245: 218Google Scholar
  77. Titmarsch S, Monk JP (1987) Terazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in essential hypertension. Drugs 33: 461–477Google Scholar
  78. U’Prichard DC, Charness ME, Robertson D, Snyder S (1978) Prazosin: differential affinities for two populations of α-adrenergic receptor binding sites. Eur J Pharmacol 50: 87PubMedCrossRefGoogle Scholar
  79. Van Brummelen P, Jie K, Timmermanns PBMWM, Van Zwieten PA (1985) Postjunctional α-adrenoceptors and the regulation of arteriolar tone in humans. J Cardiovase Pharmacol 7: S149–S152CrossRefGoogle Scholar
  80. Van Zwieten PA (1975) Antihypertensive drugs with a central action. Prog Pharmacol 1: 1–63Google Scholar
  81. Van Zwieten PA (1984) Role of α-adrenoceptors in hypertension and antihypertensive drug treatment. Am J Med 77: 17–25PubMedGoogle Scholar
  82. Van Zwieten PA, Timmermans PBMWM (1983) Cardiovascular α2-adrenoceptors. J Mol Cell Cardiol 15: 717–733PubMedCrossRefGoogle Scholar
  83. Van Zwieten PA, Timmermans PBMWM (1984) Pharmacological basis for the hypotena-Adrenoceptorsive activity and side-effects of a-methyl-DOPA, Clonidine and guanfacine. Hypertension (Suppl 6 ): 28–33Google Scholar
  84. Van Zwieten PA, De Jonge A, Wilffert B, Timmermans PBMWM, Beckeringh JJ, Thoolen MJMC (1985) Cardiovascular effects and interaction with adrenoceptors of Urapidil. Arch Int Pharmacodyn 276: 180–201PubMedGoogle Scholar
  85. Vincent J, Hamilton CA, Sumner DJ, Reid JL (1983a) A comparison of the hypotensive activity and in vitro and in vivo α-adrenoceptor antagonist properties of prazosin, trimazosin and doxazosin in the rabbit. Br J Pharmacol 79 (Suppl): 388 PGoogle Scholar
  86. Vincent J, Elliott HL, Meredith PA, Reid JL (1983b) Doxazosin, an aradrenoceptor antagonist. Pharmacokinetics and concentration effect relationships in man. Br J Clin Pharmacol 15: 719–725PubMedGoogle Scholar
  87. Wilffert B, Timmermans PBMWM, Van Zwieten PA (1982) Extrasynaptic location of α2-and non-innervated β2-adrenoceptors in the vascular system of the pithed normotensive rat. J Pharmacol Exp. Ther 221: 762–768PubMedGoogle Scholar
  88. Wood AJ, Bolli P, Simpson FO (1976) Prazosin in normal subjects: plasma levels, blood pressure and heart rate. Br J Pharmacol 3: 199–202Google Scholar
  89. Zech K, Steinijans VW, Radtke HW (1986) Pharmacokinetics of Urapidil in normal subjects. In: Amery A (ed) Treatment of hypertension with Urapidil. Roy Soc Med Serv 101: 29–38Google Scholar

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© Springer-Verlag Berlin Heidelberg 1990

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  • P. A. van Zwieten

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