Abstract
1. The effects of six β-adrenoceptive antagonists [(±)-propranolol, (+)-propranolol, (±)-sotalol, (±)-practolol, (±)-pindolol and (±)-procinolol] were studied on airway resistance and heart rate in guinea-pigs and dose-response curves constructed.
2. All β-adrenoceptive antagonists decreased heart rate and increased airway resistance. A significant correlation was found between the increase in airway resistance and the degree of bradycardia induced by all drugs except practolol. The orders of activity of the six drugs in inducing significant variations of the two parameters were respectively, for airway resistance: (±)-procinolol>(±)-pindolol>(±)-propranolol>(±)-sotalol>(+)-propranolol>(±)-practolol, and for heart rate: (±)-pindolol>(±)-procinolol>(±)-propranolol>(±)-sotalol>(+)-propranolol>(±)-practolol.
3. (±)-Sotalol, (±)-pindolol and (±)-procinolol-induced changes in airway resistance and heart rate reached plateau values, which were not modified by increasing the dose. Since sotalol and procinolol have only very weak partial agonist and cardiac depressant properties, it appears that these changes can mainly be accounted for by the suppression of sympathetic tone. It is probable that this is also the case with pindolol.
4. On the other hand, (±)-propranolol and (+)-propranolol induced dose-related changes in airway resistance and heart rate. Thus, a direct and non-specific effect of both drugs on the bronchial muscle, similar to that observed on the heart appears to be implicated, together with sympathetic tone suppression in these variations.
5. (±)-Practolol-induced effects on airway resistance and heart rate were different from those observed with the five other β-adrenoceptive antagonists.
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- AMDUR M. O., MEAD J. Mechanics of respiration in unanesthetized guinea pigs. Am J Physiol. 1958 Feb;192(2):364–368. doi: 10.1152/ajplegacy.1958.192.2.364. [DOI] [PubMed] [Google Scholar]
- Aberg G., Dzedin T., Lundholm L., Olsson L., Svedmyr N. A comparative study of some cardiovascular effects of sotalol (MJ 1999) and propranolol. Life Sci. 1969 Apr 1;8(7):353–365. doi: 10.1016/0024-3205(69)90228-8. [DOI] [PubMed] [Google Scholar]
- Areskog N. H., Adolfsson L. Effects of a cardio-selective beta-adrenergic blocker (I.C.I. 50172) at exercise in angina pectoris. Br Med J. 1969 Jun 7;2(5657):601–603. doi: 10.1136/bmj.2.5657.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrett A. M., Carter J. Comparative chronotropic activity of beta-adrenoceptive antagonists. Br J Pharmacol. 1970 Nov;40(3):373–381. doi: 10.1111/j.1476-5381.1970.tb10619.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boissier J. R., Advenier C., Giudicelli J. F., Viars P. Studies on the nature of the bronchial -adrenoreceptors. Eur J Pharmacol. 1971 Jun;15(1):101–109. doi: 10.1016/0014-2999(71)90084-7. [DOI] [PubMed] [Google Scholar]
- Boissier J. R., Giudicelli J. F., Viars P., Advenier C., Mouille P., Larno S. Studies of 1-(o-cyclopropylphenoxy)-3-isopropylamino-2-propanol, a new -adrenergic blocking drug. Eur J Pharmacol. 1971 Jul;15(2):151–159. doi: 10.1016/0014-2999(71)90166-x. [DOI] [PubMed] [Google Scholar]
- COLGAN F. J. RELATIONSHIP OF CHANGING BRONCHIAL CALIBER TO RESPIRATION IN THE DOG. J Appl Physiol. 1964 Jul;19:803–811. doi: 10.1152/jappl.1964.19.4.803. [DOI] [PubMed] [Google Scholar]
- Diamond L. On the locus of the airway constricting effect of histamine in the dog. J Pharm Pharmacol. 1969 Feb;21(2):120–121. doi: 10.1111/j.2042-7158.1969.tb08210.x. [DOI] [PubMed] [Google Scholar]
- Diamond L. Utilization of changes in pulmonary resistance for the evaluation of bronchodilator drugs. Arch Int Pharmacodyn Ther. 1967 Jul;168(1):239–250. [PubMed] [Google Scholar]
- Dunlop D., Shanks R. G. Selective blockade of adrenoceptive beta receptors in the heart. Br J Pharmacol Chemother. 1968 Jan;32(1):201–218. doi: 10.1111/j.1476-5381.1968.tb00444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giudicelli J. F., Schmitt H., Boissier J. R. Studies on dl-4-(2-hydroxy-3-isopropylaminopropoxy)-indole A/Giudicelli JF, Schmitt H, Boissier JR: Studies on dl-4-(2-hydroxy-3-isopropylaminopropoxy)-indole (LB 46), a new potent beta adrenergic blocking drug. J Pharmacol Exp Ther. 1969 Jul;168(1):116–126. [PubMed] [Google Scholar]
- Guirgis H. M. The effect of adrenergic drugs on the isolated tracheal tube in vitro and on the bronchial resistance to inflation in vivo. Arch Int Pharmacodyn Ther. 1969 Nov;182(1):147–160. [PubMed] [Google Scholar]
- Hahn R. A., Pendleton R. G., Wardell J. R., Jr A comparative study of the beta adrenergic blocking activities of propranolol and inpea. J Pharmacol Exp Ther. 1968 May;161(1):111–121. [PubMed] [Google Scholar]
- Howe R., Shanks R. G. Optical isomers of propranolol. Nature. 1966 Jun 25;210(5043):1336–1338. doi: 10.1038/2101336a0. [DOI] [PubMed] [Google Scholar]
- Ito H., Aviado D. M. Prevention of pulmonary emphysema in rats by progesterone. J Pharmacol Exp Ther. 1968 Jun;161(2):197–204. [PubMed] [Google Scholar]
- Levy J. V. Myocardial and local anesthetic actions of beta-adrenergic receptor blocking drugs: relationship to physicochemical properties. Eur J Pharmacol. 1968 Feb;2(4):250–257. doi: 10.1016/0014-2999(68)90074-5. [DOI] [PubMed] [Google Scholar]
- Lubawski I., Wale J. Studies with LB 46, a new beta-receptor blocking drug. Eur J Pharmacol. 1969;6(3):345–348. doi: 10.1016/0014-2999(69)90195-2. [DOI] [PubMed] [Google Scholar]
- MCNEILL R. S. EFFECT OF A BETA-ADRENERGIC-BLOCKING AGENT, PROPRANOLOL, ON ASTHMATICS. Lancet. 1964 Nov 21;2(7369):1101–1102. doi: 10.1016/s0140-6736(64)92617-0. [DOI] [PubMed] [Google Scholar]
- Macdonald A. G., Ingram C. G., McNeill R. S. The effect of propranolol on airway resistance. Br J Anaesth. 1967 Dec;39(12):919–926. doi: 10.1093/bja/39.12.919. [DOI] [PubMed] [Google Scholar]
- Macdonald A. G., McNeill R. S. A comparison of the effect on airway resistance of a new beta blocking drug, ICI.50,172 and propranolol. Br J Anaesth. 1968 Jul;40(7):508–510. doi: 10.1093/bja/40.7.508. [DOI] [PubMed] [Google Scholar]
- McNeill R. S., Ingram C. G. Effect of propranolol on ventilatory function. Am J Cardiol. 1966 Sep;18(3):473–475. doi: 10.1016/0002-9149(66)90072-5. [DOI] [PubMed] [Google Scholar]
- Meier J., Lydtin H., Zöllner N. Uber die Wirking von adrenergen betarezeptorenblockern auf ventilatorische Funktionen bei obstruktiven Lungenkrankheiten. Dtsch Med Wochenschr. 1966 Jan 28;91(4):145–147. doi: 10.1055/s-0028-1110536. [DOI] [PubMed] [Google Scholar]
- Moore G. E., O'Donnell S. R. A potent beta-adrenoreceptor blocking drug: 4-(2-hydroxy-3-isopropylaminopropoxy)indole. J Pharm Pharmacol. 1970 Mar;22(3):180–188. doi: 10.1111/j.2042-7158.1970.tb08494.x. [DOI] [PubMed] [Google Scholar]
- Nakano J., Kusakari T. Effect of beta adrenergic blockade on the cardiovascular dynamics. Am J Physiol. 1966 Apr;210(4):833–837. doi: 10.1152/ajplegacy.1966.210.4.833. [DOI] [PubMed] [Google Scholar]
- Oskoui M., Aviado D. M. Cardiopulmonary effects of norepinephrine and propranolol. Eur J Pharmacol. 1969 Mar;5(4):321–327. doi: 10.1016/0014-2999(69)90108-3. [DOI] [PubMed] [Google Scholar]
- Parmley W. W., Braunwald E. Comparative myocardial depressant and anti-arrhythmic properties of d-propranolol, dl-propranolol and quinidine. J Pharmacol Exp Ther. 1967 Oct;158(1):11–21. [PubMed] [Google Scholar]
- Singh B. N., Vaughan Williams E. M. A third class of anti-arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474. Br J Pharmacol. 1970 Aug;39(4):675–687. doi: 10.1111/j.1476-5381.1970.tb09893.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wale J., Pun L. Q., Rand M. J. The effects of ICI 50172, propranolol, pronethalol and MJ 1999 on beta-receptors. Eur J Pharmacol. 1969 Oct;8(1):25–35. doi: 10.1016/0014-2999(69)90125-3. [DOI] [PubMed] [Google Scholar]