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. 1987 Apr;23(4):411–423. doi: 10.1111/j.1365-2125.1987.tb03070.x

The assessment in man of the beta-adrenoceptor blocking activity and cardioselectivity of H-I 42 BS, a long acting beta-adrenoceptor blocking drug.

T H Pringle, A H Deering, M G Scott, D W Harron, R G Shanks
PMCID: PMC1386090  PMID: 2883988

Abstract

The pharmacokinetic and pharmacodynamic effects of the beta-adrenoceptor antagonist H-I 42 BS were examined in healthy subjects. In an open dose ranging study, H-I 42 BS 50, 100, 200 and 400 mg were given as single oral doses to four subjects. H-I 42 BS 400 mg caused maximum reduction in exercise heart rate (20.4 +/- 1.0%--mean +/- s.d.) at 4 h and still reduced exercise heart rate at 96 h (18.4 +/- 7.2%). Seven subjects received in double-blind, randomised order, single oral doses of H-I 42 BS 50, 100 and 200 mg, atenolol 50 and 100 mg and placebo. H-I 42 BS 400 mg was given in a single blind manner as the last dose of the study. Both H-I 42 BS and atenolol reduced supine and standing heart rate and systolic blood pressure (P less than 0.05) although atenolol had the more marked effect. The maximum percent reduction of exercise heart rate after H-I 42 BS 50 mg was 10.9 +/- 7.1%, after 100 mg was 18.7 +/- 5.8%, after 200 mg was 20.6 +/- 6.4% and after 400 mg was 21.9 +/- 8.2%. H-I 42 BS 400 mg still caused 11.0 +/- 3.5% reduction at 168 h. Atenolol 50 mg caused maximum percent reduction of exercise heart rate of 26.0 +/- 6.0% but did not reduce exercise heart rate after 24 h. The mean peak plasma concentrations for all doses of H-I 42 BS occurred at 5.1 +/- 1.5 h. The plasma elimination half-life was 47.6 +/- 8.1 h. There was a linear correlation between the dose and AUC0-infinity (r = 0.97). The cardioselectivity of H-I 42 BS and atenolol was compared. Six subjects received in double-blind random order H-I 42 BS 100 and 400 mg, atenolol 50 mg and placebo. After each dose, graded infusions of isoprenaline were given until the heart rate increased by 50 beats min-1. Dose-response curves for heart rate, diastolic blood pressure, forearm blood flow and finger tremor were constructed. There was no difference in the dose-response curves for forearm blood flow or finger tremor after H-I 42 BS 400 mg or atenolol 50 mg. Atenolol 50 mg caused more attenuation (P less than 0.01) of the diastolic blood pressure response. These results indicate that H-I 42 BS is a cardioselective beta-adrenoceptor antagonist with a long duration of action in man.

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Selected References

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  1. Arnold J. M., McDevitt D. G. Enhancement of physiological finger tremor by intravenous isoprenaline infusions in man: evaluation of its role in the assessment of beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1984 Aug;18(2):145–152. doi: 10.1111/j.1365-2125.1984.tb02446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnold J. M., O'Connor P. C., Riddell J. G., Harron D. W., Shanks R. G., McDevitt D. G. Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man. Br J Clin Pharmacol. 1985 May;19(5):619–630. doi: 10.1111/j.1365-2125.1985.tb02689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balnave K., Neill J. D., Russell C. J., Harron D. W., Leahey W. J., Wilson R., Shanks R. G. Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta-adrenoceptor blocking drug. Br J Clin Pharmacol. 1981 Feb;11(2):171–180. doi: 10.1111/j.1365-2125.1981.tb01121.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beresford R., Heel R. C. Betaxolol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension. Drugs. 1986 Jan;31(1):6–28. doi: 10.2165/00003495-198631010-00002. [DOI] [PubMed] [Google Scholar]
  5. Braunwald E. Symposium on beta adrenergic receptor blockade. An editorial introduction to the symposium. Am J Cardiol. 1966 Sep;18(3):303–307. doi: 10.1016/0002-9149(66)90046-4. [DOI] [PubMed] [Google Scholar]
  6. GREENFIELD A. D. Venous occlusion plethysmography. Methods Med Res. 1960;8:293–301. [PubMed] [Google Scholar]
  7. Harms H. H., Gooren L., Spoelstra A. J., Hesse C., Verschoor L. Blockade of isoprenaline-induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects, by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol. Br J Clin Pharmacol. 1978 Jan;5(1):19–26. doi: 10.1111/j.1365-2125.1978.tb01593.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jackisch R., Lederle M., Hertting G. Radioligand binding studies with 3-(4-(2-hydroxy-3-((1, 1-dimethylethyl)-amino)-propoxy)-phenyl)-7-methoxy-2-methyl- 1(2H)-isoquinolinone (HI-42), a new cardioselective beta-adrenoceptor blocker with long-lasting effects in vivo. Arzneimittelforschung. 1985;35(1A):237–240. [PubMed] [Google Scholar]
  9. Leitch A. G., Clancy L. J., Costello J. F., Flenley D. C. Effect of intravenous infusion of salbutamol on ventilatory response to carbon dioxide and hypoxia and on heart rate and plasma potassium in normal men. Br Med J. 1976 Feb 14;1(6006):365–367. doi: 10.1136/bmj.1.6006.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. McDevitt D. G. The assessment of beta-adrenoceptor blocking drugs in man. Br J Clin Pharmacol. 1977 Aug;4(4):413–425. doi: 10.1111/j.1365-2125.1977.tb00756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. O'Connor P. C., Arnold J. M., Brown A. N., Francis R. J., Finch M. B., Galloway D. B., Harron D. W., McDevitt D. G., Shanks R. G. Human pharmacokinetic and pharmacodynamic studies on Ro31-1118, a new beta-adrenoceptor antagonist. Br J Clin Pharmacol. 1985 Mar;19(3):319–327. doi: 10.1111/j.1365-2125.1985.tb02650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Phillips P. J., Vedig A. E., Jones P. L., Chapman M. G., Collins M., Edwards J. B., Smeaton T. C., Duncan B. M. Metabolic and cardiovascular side effects of the beta 2-adrenoceptor agonists salbutamol and rimiterol. Br J Clin Pharmacol. 1980 May;9(5):483–491. doi: 10.1111/j.1365-2125.1980.tb05844.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shanks R. G. The properties of beta-adrenoceptor antagonists. Postgrad Med J. 1976;52 (Suppl 4):14–20. [PubMed] [Google Scholar]
  15. William-Olsson T., Fellenius E., Björntorp P., Smith U. Differences in metabolic responses to beta-adrenergic stimulation after propranolol or metoprolol administration. Acta Med Scand. 1979;205(3):201–206. doi: 10.1111/j.0954-6820.1979.tb06031.x. [DOI] [PubMed] [Google Scholar]

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