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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 339, Issue 4, pp 474–478 | Cite as

Stereoselective hemodynamic effects of (R)-and (S)-propranolol in man

  • Kurt Stoschitzky
  • Wolfgang Lindner
  • Monika Rath
  • Christa Leitner
  • Georg Uray
  • aGerald Zernig
  • Thomas Moshammer
  • Werner Klein
Article

Summary

In a randomized, double-blind, placebo-controlled, cross-over study 24 healthy volunteers were examined before and 2 h after oral administration of 80 mg (R,S)-, 40 mg (R)- and 40 mg (S)-propranolol · HCI; 8 of them received placebo in an additional run. During exercise on a bicycle ergometer and a rest period the rate pressure product was decreased by 80 mg (R,S)-propranolol · HCl (−32.8%p < 0.0001) and 40 mg (S)-propranolol · HCl (−32.3%;p < 0.0001), whera 40 mg (R)-propranolol · HCl as well as placebo showed no effect. corresponding binding inhibition experiments using (−)-(125I)iodocyanopindolol in a sarcolemma-enriched cardiac membrane preparation yielded a eudismic ratio of 179 for (S)- over (R)-propranolol. 2 h after oral application, stereospecific HPLC analysis revealed different individual concentrations in plasma of (R)-(22.3 ± 21.7 ng/ml) and (S)-propranolol (30.4 ± 26.9 ng/ml) when 80 mg of (R,S)-propranolol · Hcl was administered. The plasma levels were similar when 40 mg of the pure enantiomer of (R)- (22.7 ± 20.3 ng/ml) or (S)-propranolol · HCl (28.7 ± 22.5 ng/ml) was applied. (R)- and (S)-propranolol are two substances with different pharmacodynamic and pharmacokinetic properties. As there are methods available to produce the optically pure enantiomers, they should be used rather than the racemic mixture.

Key words

(R)-Propranolol (S)-Propranolol Betaadrenoceptor antagonists Stereoselectivity Iodocyanopindolol 

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References

  1. Alkondon M, Ray A, Sen P (1986) Autonomic regulation involved in the ocular hypotensive action of beta-adrenergic blocking agents. J Pharm Pharmacol 38:319–322Google Scholar
  2. Ariens EJ, Wuis EW, Veringa EJ (1988) Stereoselectivity of bioactive xenobiotics. Biochem Pharmacol 37:9–18Google Scholar
  3. Barrett AM, Cullum VA (1968) The biological properties of the optical enantiomers of propranolol and their effects on cardiac arrhythmias. Br J Pharmacol 34:43–55Google Scholar
  4. Bonacker O, Glossmann H (1981) Mammalian β-adrenoceptors: Concomitant biospecific elution with protein kinase activity from sepharose-alprenolol. Eur J Pharmacol 75:197–204Google Scholar
  5. Brodde OE, Engel G, Hoyer D, Bock KD, Weber F (1981) The β-adrenergic receptor in human lymphocytes: Subclassification by the use of a new radio-ligand, (±)-[125I]iodocyanopindolol. Life Sci 29:2189–2198Google Scholar
  6. Buchinger W, Lindner W, Lind P, Rath M, Langsteger W, Klima G, Költringer P, Eber O (1988) Wirkung von (R)- versus (S)-Propranolol auf den peripheren Schilddrüsenhormonstoffwechsel hyperthyreoter Patienten. 2nd Thyroid Symposium, Peripheral Thyroid Hormone Metabolism April 28–30, 1988. Acta Med Aust (Sonderheft 1):61–62Google Scholar
  7. Delavier-Klutchko C, Hoebeke J, Strosberg AD (1984) The human carcinoma cell line A431 possesses large number of functional β-adrenergic receptors. FEBS Lett 169:151–155Google Scholar
  8. Elkins RP, Kelly JF, Rosenberg BJ (1986) A radioreceptor assay in which iodocyanopindolol is used to determine propranolol and its active metabolites in unextracted serum or plasma. Clin Chem 32:180–183Google Scholar
  9. Engel G, Hoyer D, Berthold R, Wagner H (1981) (+)-[125Iodo]cy-anopindolol, a new ligand for beta-adrenoceptors: Identification and quantitation of subclasses of beta-adrenoceptors in guinea-pig. Naunyn-Schmiedeberg's Arch Pharmacol 317: 277–285Google Scholar
  10. Frishman WH, Teicher M (1985) Beta-adrenergic blockade. Cardiology 72:280–296Google Scholar
  11. Glossmann H, Ferry DR (1985) Assay for calcium channels. Meth Enzymol 109:513–550Google Scholar
  12. Heyma P, Larkins RG, Higginbotham, L, Wahng K (1980)D-Propranolol andDL-propranolol both decrease conversion ofL-thyroxine andL-triiodothyronine. Br Med J 281:24–25Google Scholar
  13. Howe R, Shanks RG (1966) Optical isomers of propranolol. Nature 210:1336 -1338Google Scholar
  14. Hoyer D, Engel G, Berthold R (1082) Binding characteristics of (+)-, (±)- and (−)-(125iodo)cyanopindolol to guinea-pig left ventricle membranes. Naunyn-Schmiedeberg's Arch Pharmacol 318:319–329Google Scholar
  15. Kendall MJ, Beeley M (1983) Beta-adrenoceptor blocking drugs: Adverse reactions and drug interactions. Pharmacol Ther 21:351–369Google Scholar
  16. Linden J (1982) Calculating the dissociation constant of an unlabeled compound from the concentration required to displace radiolabel binding by 50%. J Cycl Nucl Res 8:163–172Google Scholar
  17. Lindner W (1987) U.S. Patent 4,652,672Google Scholar
  18. Lindner W, Leitner Ch, Uray G (1984) Liquid chromatographic separation of enantiomeric alkanolamines via diastereomeric tartaric acid monoesters. J Chromatogr 316:605–616Google Scholar
  19. Rahn KH (1983) Haemodynamic effects of the optical isomers of beta-receptor blocking agents. Eur Heart J 4 (Suppl D):27–30Google Scholar
  20. Rahn KH, Hawlina A, Kersting F, Planz G (1974) Studies on the antihypertensive action of the optical isomers of propranolol in man. Naunyn-Schmiedeberg's Arch Pharmacol 286:319–323Google Scholar
  21. Stensrud P, Sjaastad O (1976) Short-term clinical trial of propranolol in racemic form (Inderal)-d-propranolol, and placebo in migraine. Acta Neurol Scand 55:229–232Google Scholar
  22. Vale J, Phillips CI (1970). Effect ofdl- andd-propranolol on ocular tension in rabbits and patients. Exptl Eye Res 9:82–90Google Scholar
  23. Walle T, Webb JG, Bagwell EE, Walle UK, Daniell HB, Gaffney TE (1988) Stereoselective delivery and actions of beta receptor antagonist. Biochem Pharmacol 37:115–124Google Scholar
  24. Zernig G, Glossmann H (1988) A novel 1,4-dihydropyridine-binding site on mitochondrial membranes from guinea-pig heart, liver and kidney. Biochem J 253:49–58Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Kurt Stoschitzky
    • 1
  • Wolfgang Lindner
    • 2
  • Monika Rath
    • 2
  • Christa Leitner
    • 2
  • Georg Uray
    • 3
  • aGerald Zernig
    • 4
  • Thomas Moshammer
    • 4
  • Werner Klein
    • 1
  1. 1.Department KardiologieMedizinische Universitätsklinik GrazGrazAustria
  2. 2.Institut für Pharmazeutische ChemieUniversität GrazGrazAustria
  3. 3.Institut für Organische ChemicUniversität GrazGrazAustria
  4. 4.Institut für Biochemische PharmakologieUniversität InnsbruckInnsbruckAustria

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