Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1982;13(Suppl 2):187S–192S. doi: 10.1111/j.1365-2125.1982.tb01909.x

Pindolol--a beta-adrenoceptor blocking drug with partial agonist activity: clinical pharmacological considerations.

W H Aellig
PMCID: PMC1402142  PMID: 6125169

Abstract

1 Pindolol is a beta-adrenoceptor antagonist equally effective on beta 1- and beta 2-adrenoceptors which has a relatively long duration of action. It is practically completely absorbed and, unlike most other beta-adrenoceptor blockers, is only metabolized to a small extent during the first passage through the liver. 2 Pindolol possesses partial agonist activity (intrinsic sympathomimetic activity, ISA). This means that apart from blocking beta-adrenoceptors it produces some stimulation. Pindolol therefore only slightly influences normal sympathetic drive at rest but effectively reduces the effects of elevated sympathetic activity. 3 Various therapeutic advantages have been attributed to the partial agonist activity of pindolol: no or only slight alterations in normal cardiac output, heart rate and peripheral blood flow occur. Peripheral resistance is reduced during chronic oral therapy. No alteration of HDL/LDL cholesterol ratio has been observed. Rebound phenomena on sudden withdrawal of therapy and bronchoconstriction in susceptible patients are less likely than with drugs devoid of ISA.

Full text

PDF
188S

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aarons R. D., Nies A. S., Gal J., Hegstrand L. R., Molinoff P. B. Elevation of beta-adrenergic receptor density in human lymphocytes after propranolol administration. J Clin Invest. 1980 May;65(5):949–957. doi: 10.1172/JCI109781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aellig W. H. Activity and duration of action of pindolol and alprenolol compared in healthy volunteers. Eur J Clin Pharmacol. 1978 Dec 18;14(5):305–308. doi: 10.1007/BF00611898. [DOI] [PubMed] [Google Scholar]
  3. Aellig W. H. Comparison of the duration of action of pindolol and slow release oxprenolol in healthy volunteers. Eur J Clin Pharmacol. 1978 Nov 27;14(3):167–169. doi: 10.1007/BF02089955. [DOI] [PubMed] [Google Scholar]
  4. Aellig W. H. Duration of action and plasma levels of beta-adrenoceptor blocking drugs. Arch Int Pharmacodyn Ther. 1980;Suppl:32–37. [PubMed] [Google Scholar]
  5. Aellig W. H. Investigations with beta-adrenoceptor blocking drugs in healthy volunteers. Acta Med Scand Suppl. 1977;606:71–75. doi: 10.1111/j.0954-6820.1977.tb18032.x. [DOI] [PubMed] [Google Scholar]
  6. Aellig W. H. Klinisch-pharmakologische Untersuchungen mit Pindolol nach intravenöser und oraler Verabreichung. Adv Clin Pharmacol. 1976;11:9–13. [PubMed] [Google Scholar]
  7. Aellig W. H. beta-Adrenoceptor blocking activity and duration of action of pindolol and propranolol in healthy volunteers. Br J Clin Pharmacol. 1976 Apr;3(2):251–257. doi: 10.1111/j.1365-2125.1976.tb00600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Arstila M., Kallio V., Wendelin H. Propranolol and LB 46 (prinodolol) in angina pectoris. A comparative long-term ergometric study. Ann Clin Res. 1973 Apr;5(2):91–100. [PubMed] [Google Scholar]
  9. Atterhög J. H., Dunér H., Pernow B. Experience with pindolol, a betareceptor blocker, in the treatment of hypertension. Am J Med. 1976 May 31;60(6):872–876. doi: 10.1016/0002-9343(76)90907-4. [DOI] [PubMed] [Google Scholar]
  10. Atterhög J. H., Dunér H., Pernow B. Hemodynamic effect of long--term treatment with pindolol in essential hypertension with special reference to the resistance and capacitance vessels of the forearm. Acta Med Scand. 1977;202(6):517–521. doi: 10.1111/j.0954-6820.1977.tb16874.x. [DOI] [PubMed] [Google Scholar]
  11. Carruthers S. G., Kelly J. G., McDevitt D. G., Shanks R. G. Blood levels of practolol after oral and parenteral administration and their relationship to exercise heart rate. Clin Pharmacol Ther. 1974 May;15(5):497–509. doi: 10.1002/cpt1974155497. [DOI] [PubMed] [Google Scholar]
  12. Clark B. J., Menninger K., Bertholet A. Pindolol--the pharmacology of a partial agonist. Br J Clin Pharmacol. 1982;13(Suppl 2):149S–158S. doi: 10.1111/j.1365-2125.1982.tb01904.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Clark B., Saameli K. Pharmacological properties of a new beta-receptor blocking agent. Triangle. 1970;9(8):300–308. [PubMed] [Google Scholar]
  14. Coltart D. J., Shand D. G. Plasma propranolol levels in the quaniitative assessment of beta-adrenergic blockade in man. Br Med J. 1970 Sep 26;3(5725):731–734. doi: 10.1136/bmj.3.5725.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dorow P. Influence of intrinsic sympathomimetic activity (ISA) during beta-adrenoceptor blockade in asthmatics. Br J Clin Pharmacol. 1982;13(Suppl 2):321S–323S. doi: 10.1111/j.1365-2125.1982.tb01936.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dufour R., Scazziga B., Schelling J. L. Acute circulatory effects of a beta adrenergic blocking agent (LB 46) in patients with sympathetic overstimulation. Int Z Klin Pharmakol Ther Toxikol. 1970 Dec;4(1):145–147. [PubMed] [Google Scholar]
  17. Frishman W., Kostis J., Strom J., Hossler M., Elkayam U., Goldner S., Silverman R., Davis R., Weinstein J., Sonnenblick E. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 6. A comparison of pindolol and propranolol in treatment of patients with angina pectoris. The role of intrinsic sympathomimetic activity. Am Heart J. 1979 Oct;98(4):526–535. doi: 10.1016/0002-8703(79)90261-8. [DOI] [PubMed] [Google Scholar]
  18. Gugler R., Bodem G. Single and multiple dose pharmacokinetics of pindolol. Eur J Clin Pharmacol. 1978 Mar 17;13(1):13–16. doi: 10.1007/BF00606675. [DOI] [PubMed] [Google Scholar]
  19. Gugler R. The pharmacokinetic properties of beta adrenoceptor blocking drugs. Arch Int Pharmacodyn Ther. 1980;Suppl:27–31. [PubMed] [Google Scholar]
  20. Harry J. D., Knapp M. F., Linden R. J., Newcombe C. P., Stoker J. B. A test which may demonstrate in man, intrinsic sympathomimetic activity of beta-adrenoceptor blocking drugs [proceedings]. Br J Clin Pharmacol. 1975 Aug;2(4):374P–374P. [PubMed] [Google Scholar]
  21. Hill R. C., Turner P. Preliminary investigations of a new beta-adrenoceptive receptor blocking drug, LB46, in man. Br J Pharmacol. 1969 Jun;36(2):368–372. doi: 10.1111/j.1476-5381.1969.tb09511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jennings G., Bobik A., Korner P. Influence of intrinsic sympathomimetic activity of beta-adrenoceptor blockers on the heart rate and blood pressure responses to graded exercise. Br J Clin Pharmacol. 1981 Sep;12(3):355–362. doi: 10.1111/j.1365-2125.1981.tb01226.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lehtonen A., Hietanen E., Marniemi J., Peltonen P., Niskanen J. Effect of pindolol on serum lipids and lipid metabolizing enzymes. Br J Clin Pharmacol. 1982;13(Suppl 2):445S–447S. doi: 10.1111/j.1365-2125.1982.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lehtonen A., Viikari J. Long-term effect of sotalol on plasma lipids. Clin Sci (Lond) 1979 Dec;57 (Suppl 5):405s–407s. doi: 10.1042/cs057405s. [DOI] [PubMed] [Google Scholar]
  25. Leren P., Foss P. O., Helgeland A., Hjermann I., Holme I., Lund-Larsen P. G. Effect of propranolol and prazosin on blood lipids. The Oslo Study. Lancet. 1980 Jul 5;2(8184):4–6. doi: 10.1016/s0140-6736(80)92888-3. [DOI] [PubMed] [Google Scholar]
  26. Lima D. R., Kilfeather S., Hedges A., Turner P. Comparison of four different beta-adrenoceptor blocking drugs on lymphocyte isoprenaline-stimulated cyclic AMP production. Br J Clin Pharmacol. 1981 Jun;11(6):555–559. doi: 10.1111/j.1365-2125.1981.tb01170.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lima D. R., Turner P. Partial agonist activity of practolol on human lymphocyte cyclic AMP production. Br J Clin Pharmacol. 1981 May;11(5):521–521. doi: 10.1111/j.1365-2125.1981.tb01161.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Louis W. J., McNeil J. J. Beta-adrenoceptor blocking drugs: the relevance of intrinsic sympathomimetic activity. Br J Clin Pharmacol. 1982;13(Suppl 2):317S–320S. doi: 10.1111/j.1365-2125.1982.tb01935.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Man In'T Veld A. J., Schalekamp M. A. Pindolol acts as beta-adrenoceptor agonist in orthostatic hypotension. Br Med J (Clin Res Ed) 1981 Aug 22;283(6290):561–561. doi: 10.1136/bmj.283.6290.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Man in 't Veld A. J., Schalekamp M. A. Pindolol acts as beta-adrenoceptor agonist in orthostatic hypotension: therapeutic implications. Br Med J (Clin Res Ed) 1981 Mar 21;282(6268):929–931. doi: 10.1136/bmj.282.6268.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. McDevitt D. G., Brown H. C., Carruthers S. G., Shanks R. G. Influence of intrinsic sympathomimetic activity and cardioselectivity on beta adrenoceptor blockade. Clin Pharmacol Ther. 1977 May;21(5):556–566. doi: 10.1002/cpt1977215556. [DOI] [PubMed] [Google Scholar]
  32. McNeil J. J., Louis W. J., Doyle A. E., Vajda F. J. Comparison of metoprolol and pindolol in the treatment of mild to moderate hypertension: a double-blind crossover study. Med J Aust. 1979 May 19;1(10):431-2, 461. doi: 10.5694/j.1326-5377.1979.tb127016.x. [DOI] [PubMed] [Google Scholar]
  33. Meier J., Nüesch E. Pindolol, a beta-adrenoceptor blocking agent with a negligible first-pass effect. Br J Clin Pharmacol. 1977 Jun;4(3):371–372. doi: 10.1111/j.1365-2125.1977.tb00726.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Miettinen T. A., Vanhanen H., Huttunen J. K., Naukkarinen V., Mattila S., Strandberg T., Kumlin T. HDL cholesterol and beta-adrenoceptor blocking agents in a 5 year multifactorial primary prevention trial. Br J Clin Pharmacol. 1982;13(Suppl 2):431S–434S. doi: 10.1111/j.1365-2125.1982.tb01952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nyberg G. Pindolol in orthostatic hypotension. Br Med J (Clin Res Ed) 1981 May 23;282(6277):1704–1704. doi: 10.1136/bmj.282.6277.1704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nyberg G., Wilhelmsson C., Vedin A. Intrinsic sympathomimetic activity of penbutolol. Eur J Clin Pharmacol. 1979;16(6):381–386. doi: 10.1007/BF00568197. [DOI] [PubMed] [Google Scholar]
  37. Ohlsson O., Lindell S. E. The effects of pindolol and prazosin on hand blood flow in patients with cold extremities and on treatment with beta-blockers. Acta Med Scand. 1981;210(3):217–219. doi: 10.1111/j.0954-6820.1981.tb09804.x. [DOI] [PubMed] [Google Scholar]
  38. Prichard B. N., Walden R. J. The syndrome associated with the withdrawal of beta-adrenergic receptor blocking drugs. Br J Clin Pharmacol. 1982;13(Suppl 2):337S–343S. doi: 10.1111/j.1365-2125.1982.tb01938.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rosenthal J., Kaiser H., Raschig A., Welzel D. Treatment of hypertension with a beta-adrenoceptor blocker. A multicentre trial with pindolol. Br J Clin Pract. 1979 Jun;33(6):165-74, 181. [PubMed] [Google Scholar]
  40. Rumboldt Z., Fanciullacci M., Franchi G., Sicuteri F. Farmacologia clinica del pindololo sui recettori venomotori. Boll Soc Ital Biol Sper. 1975 Jul 30;51(14):895–900. [PubMed] [Google Scholar]
  41. Schlüter K. J., Aellig W. H., Petersen K. G., Rieband H. C., Wehrli A., Kerp L. The influence of beta-adrenoceptor blocking drugs with and without intrinsic sympathomimetic activity on the hormonal responses to hypo- and hyperglycaemia. Br J Clin Pharmacol. 1982;13(Suppl 2):407S–417S. doi: 10.1111/j.1365-2125.1982.tb01948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Svendsen T. L., Hartling O. J., Trap-Jensen J., McNair A., Bliddal J. Adrenergic beta receptor blockade: hemodynamic importance of intrinsic sympathomimetic activity at rest. Clin Pharmacol Ther. 1981 Jun;29(6):711–718. doi: 10.1038/clpt.1981.100. [DOI] [PubMed] [Google Scholar]
  43. Svendsen T. L., Rasmussen S., Hartling O. J., Nielsen P. E., Trap-Jensen J. Acute and long-term effects of labetalol on systemic and pulmonary haemodynamics in hypertensive patients. Eur J Clin Pharmacol. 1980 Jan;17(1):5–11. doi: 10.1007/BF00561670. [DOI] [PubMed] [Google Scholar]
  44. Szécsi E., Kohlschütter S., Schiess W., Lang E. Abrupt withdrawal of pindolol or metoprolol after chronic therapy. Br J Clin Pharmacol. 1982;13(Suppl 2):353S–357S. doi: 10.1111/j.1365-2125.1982.tb01940.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tanaka N., Sakaguchi S., Oshige K., Niimura T., Kanehisa T. Effect of chronic administration of propranolol on lipoprotein composition. Metabolism. 1976 Oct;25(10):1071–1075. doi: 10.1016/0026-0495(76)90014-7. [DOI] [PubMed] [Google Scholar]
  46. Waal-Manning H. J. The antihypertensive action of several beta-adrenoreceptor-blocking drugs. N Z Med J. 1976 Apr 14;83(561):223–226. [PubMed] [Google Scholar]
  47. Wainer E., Boner G., Rosenfeld J. B. Effects of pindolol on renal function. Clin Pharmacol Ther. 1980 Nov;28(5):575–580. doi: 10.1038/clpt.1980.205. [DOI] [PubMed] [Google Scholar]
  48. Weil C., Waite R. Haemodynamic differences in untreated hypertension and hypertension treated with various beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1982;13(Suppl 2):279S–283S. doi: 10.1111/j.1365-2125.1982.tb01925.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wilcox C. S., Lewis P. S., Peart W. S., Sever P. S., Osikowska B. A., Suddle S. A., Bluhm M. M., Veall N., Lancaster R. Renal function, body fluid volumes, renin, aldosterone, and noradrenaline during treatment of hypertension with pindolol. J Cardiovasc Pharmacol. 1981 May-Jun;3(3):598–611. doi: 10.1097/00005344-198105000-00018. [DOI] [PubMed] [Google Scholar]
  50. Yaari S., Goldbourt, Even-Zohar S., Neufeld H. N. Associations of serum high density lipoprotein and total cholesterol with total, cardiovascular, and cancer mortality in a 7-year prospective study of 10 000 men. Lancet. 1981 May 9;1(8228):1011–1015. doi: 10.1016/s0140-6736(81)92184-x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES