Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1970 Apr;38(4):749–757. doi: 10.1111/j.1476-5381.1970.tb09884.x

Local anaesthetic and anti-arrhythmic actions of alprenolol relative to its effect on intracellular potentials and other properties of isolated cardiac muscle

B N Singh, E M Vaughan Williams
PMCID: PMC1702589  PMID: 4392560

Abstract

1. Alprenolol, a β-adrenoceptor blocking drug reported to have the same potency as propranolol in vitro and in vivo, was found to be four times more active than procaine as a local anaesthetic on frog sciatic nerve.

2. At doses of 0·125 mg/kg and above alprenolol protected anaesthetized guinea-pigs against ouabain-induced ventricular fibrillation.

3. In isolated rabbit atria, resting potentials were unchanged, and the duration of the action potential was not prolonged, by concentrations of alprenolol up to 10·5 × 10-6M. The maximum rate of depolarization (MRD), however, was reduced by 30% at a concentration of 0·525 × 10-6M. This was 214 times less than the concentration which reduced the frog action potential height by 25%.

4. The concentration of alprenolol required to produce more than 15% decrease in contraction or maximum driven frequency was 3·5 × 10-6M.

5. As a test of the direct action of alprenolol on isolated cardiac muscle, MRD was also a more sensitive test than the measurement of electrical threshold or conduction velocity.

Full text

PDF
749

Selected References

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

  1. Ablad B., Brogård M., Ek L. Pharmacological properties of H 56-28--a beta-adrenergic receptor antagonist. Acta Pharmacol Toxicol (Copenh) 1967;25:9–40. [PubMed] [Google Scholar]
  2. Brading A., Bülbring E., Tomita T. The effect of sodium and calcium on the action potential of the smooth muscle of the guinea-pig taenia coli. J Physiol. 1969 Feb;200(3):637–654. doi: 10.1113/jphysiol.1969.sp008713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dohadwalla A. N., Freedberg A. S., Vaughan Williams E. M. The relevance of beta-receptor blockade to ouabain-induced cardiac arrhythmias. Br J Pharmacol. 1969 Jun;36(2):257–267. doi: 10.1111/j.1476-5381.1969.tb09503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dudel J., Peper K., Rüdel R., Trautwein W. Effect of tetrodotoxin on membrane currents in mammalian cardiac fibres. Nature. 1967 Jan 21;213(5073):296–297. doi: 10.1038/213296a0. [DOI] [PubMed] [Google Scholar]
  5. Forsberg S. A., Johnsson G. Hemodynamic effects of propranolol and H 56-28 in man--comparative study of two beta-adrenergic receptor antagonists. Acta Pharmacol Toxicol (Copenh) 1967;25:75–83. doi: 10.1111/j.1600-0773.1967.tb02998.x. [DOI] [PubMed] [Google Scholar]
  6. Johnsson G., Norrby A., Sölvell L. Potency and time effect relationship in man of propranolol and H 56-28. I. Comparative studies after intravenous administration. II. Studies on the ratio of equipotent oral and intravenous doses. Acta Pharmacol Toxicol (Copenh) 1967;25:95–105. doi: 10.1111/j.1600-0773.1967.tb03000.x. [DOI] [PubMed] [Google Scholar]
  7. Johnsson G. The effects of intra-arterially administered propranolol and H 56-28 on blood flow in the forearm--a comparative study of two beta-adrenergic receptor antagonists. Acta Pharmacol Toxicol (Copenh) 1967;25:63–74. doi: 10.1111/j.1600-0773.1967.tb02997.x. [DOI] [PubMed] [Google Scholar]
  8. McAllister R. E., Noble D. The effect of subthreshold potentials on the membrane current in cardiac Purkinje fibres. J Physiol. 1967 May;190(2):381–387. doi: 10.1113/jphysiol.1967.sp008216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. NOBLE D. A modification of the Hodgkin--Huxley equations applicable to Purkinje fibre action and pace-maker potentials. J Physiol. 1962 Feb;160:317–352. doi: 10.1113/jphysiol.1962.sp006849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Noble D. Applications of Hodgkin-Huxley equations to excitable tissues. Physiol Rev. 1966 Jan;46(1):1–50. doi: 10.1152/physrev.1966.46.1.1. [DOI] [PubMed] [Google Scholar]
  11. Noble D., Tsien R. W. Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres. J Physiol. 1969 Jan;200(1):205–231. doi: 10.1113/jphysiol.1969.sp008689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Papp J. G., Williams E. M. A comparison of the anti-arrhythmic actions of I.C.I. 50172 and (--)-propranolol and their effects on intracellular cardiac action potentials and other features of cardiac function. Br J Pharmacol. 1969 Oct;37(2):391–399. doi: 10.1111/j.1476-5381.1969.tb10576.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Reuter H. The dependence of slow inward current in Purkinje fibres on the extracellular calcium-concentration. J Physiol. 1967 Sep;192(2):479–492. doi: 10.1113/jphysiol.1967.sp008310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. VAUGHAN WILLIAMS E. M. The effect of changes in extracellular potassium concentration on the intracellular potentials of isolated rabbit atria. J Physiol. 1959 Jun 11;146(3):411–428. doi: 10.1113/jphysiol.1959.sp006201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. VAUGHAN WILLIAMS E. M. The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records. Br J Pharmacol Chemother. 1958 Sep;13(3):276–287. doi: 10.1111/j.1476-5381.1958.tb00903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. WILLIAMS E. M., SEKIYA A. Prevention of arrhythmias due to cardiac glycosides by block of sympathetic beta receptors. Lancet. 1963 Feb 23;1(7278):420–421. doi: 10.1016/s0140-6736(63)92306-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES