Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1980 Jan;68(1):75–82. doi: 10.1111/j.1476-5381.1980.tb10701.x

β-Adrenoceptor antagonists: studies on behaviour (delayed differentiation) in the monkey (Macaca mulatta)

AN Nicholson, Catherine M Wright
PMCID: PMC2044090  PMID: 6101977

Abstract

1 Activity of six β-adrenoceptor antagonists was studied on behavioural activity (delayed differentiation) in the monkey (Macaca mulatta). The drugs, three relatively lipophilic antagonists (propranolol, oxprenolol and metoprolol), and three relatively hydrophilic antagonists (acebutolol, atenolol and sotalol), were given by intraperitoneal injection (5 to 30 mg/kg).

2 With atenolol (25 to 30 mg/kg), total response time was increased, but there was no effect on the number of correct responses. With acebutolol (25 to 30 mg/kg), the number of correct responses was reduced, but there was no effect on total response time. With metoprolol (25 to 30 mg/kg), there was an increase in total response time and a decrease in the number of correct responses, and correct responses were decreased 4 h after injection over the whole dose range (5 to 30 mg/kg).

3 Some animals failed to respond or complete the task with 30 mg/kg oxprenolol, 25 mg/kg sotalol and 20 mg/kg propranolol. With 25 mg/kg oxprenolol, the total response time was increased and the number of correct responses was decreased. With 5-20 mg/kg sotalol, total response time was increased, but there was no effect on the number of correct responses. With 15 mg/kg of (±)-propranolol and its isomers, there were increases in total response time and decreases in correct responses.

4 The studies suggest that lipophilic antagonists, such as propranolol, oxprenolol and metoprolol, are likely to have, at least, effects on the central nervous system, while hydrophilic antagonists may modify the peripheral nervous system. In the dose-ranges studied, propranolol had the greatest, and atenolol and acebutolol had the least effects. Atenolol and acebutolol may prove to be particularly useful in man when disturbances of the nervous system are to be avoided.

Full text

PDF
82

Selected References

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

  1. Alexander R. W., Davis J. N., Lefkowitz R. J. Direct identification and characterisation of beta-adrenergic receptors in rat brain. Nature. 1975 Dec 4;258(5534):437–440. doi: 10.1038/258437a0. [DOI] [PubMed] [Google Scholar]
  2. Bainbridge J. G., Greenwood D. T. Tranquillizing effects of propranolol demonstrated in rats. Neuropharmacology. 1971 Jul;10(4):453–458. doi: 10.1016/0028-3908(71)90073-6. [DOI] [PubMed] [Google Scholar]
  3. Barrett A. M., Nunn B. Adrenergic neuron blocking properties of (plus or minus)-propranolol and (plus)-propranolol. J Pharm Pharmacol. 1970 Nov;22(11):806–810. doi: 10.1111/j.2042-7158.1970.tb08443.x. [DOI] [PubMed] [Google Scholar]
  4. Brown H. C., Carruthers S. G., Kelly J. G., McDevitt D. G., Shanks R. G. Observations on the efficacy and pharmacokinetics of sotalol after oral administration. Eur J Clin Pharmacol. 1976 Mar 22;09(5-6):367–372. doi: 10.1007/BF00606550. [DOI] [PubMed] [Google Scholar]
  5. Davis W. G. A comparison of the local anaesthetic-, "quinidine-like"- and adrenergic beta-blocking-activities of five beta-receptor antagonists. J Pharm Pharmacol. 1970 Apr;22(4):284–290. doi: 10.1111/j.2042-7158.1970.tb08520.x. [DOI] [PubMed] [Google Scholar]
  6. Delini-Stula A., Meier M. Inhibitory effects of propranolol and oxprenolol on excitation induced by a MAO inhibitor and reserpine in the mouse. Neuropharmacology. 1976 Jul;15(7):383–388. doi: 10.1016/0028-3908(76)90113-1. [DOI] [PubMed] [Google Scholar]
  7. Direct evidence for an interaction of beta-adrenergic blockers with the 5-HT receptor. Nature. 1977 May 19;267(5608):289–290. doi: 10.1038/267289a0. [DOI] [PubMed] [Google Scholar]
  8. Eliash S., Weinstock M. Role of adrenergic neurone blockade in the hypotensive action of propranolol. Br J Pharmacol. 1971 Oct;43(2):287–294. [PMC free article] [PubMed] [Google Scholar]
  9. Garvey H. L., Ram N. Centrally induced hypotensive effects of beta-adrenergic blocking drugs. Eur J Pharmacol. 1975 Sep-Oct;33(2):283–294. doi: 10.1016/0014-2999(75)90172-7. [DOI] [PubMed] [Google Scholar]
  10. Garvey H. L., Ram N. Comparative antihypertensive effects and tissue distribution of beta adrenergic blocking drugs. J Pharmacol Exp Ther. 1975 Jul;194(1):220–233. [PubMed] [Google Scholar]
  11. Green A. R., Grahame-Smith D. G. (-)-Propranolol inhibits the behavioural responses of rats to increased 5-hydroxytryptamine in the central nervous system. Nature. 1976 Aug 12;262(5569):594–596. doi: 10.1038/262594a0. [DOI] [PubMed] [Google Scholar]
  12. Hayes A., Cooper R. G. Studies on the absorption, distribution and excretion of propranolol in rat, dog and monkey. J Pharmacol Exp Ther. 1971 Feb;176(2):302–311. [PubMed] [Google Scholar]
  13. Hermansen K. Effect of different beta-adrenergic receptor blocking agents on hexobarbital induced narcosis in mice. Acta Pharmacol Toxicol (Copenh) 1969;27(6):453–460. doi: 10.1111/j.1600-0773.1969.tb00493.x. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Laverty R., Taylor K. M. Propranolol uptake into the central nervous system and the effect on rat behaviour and amine metabolism. J Pharm Pharmacol. 1968 Aug;20(8):605–609. doi: 10.1111/j.2042-7158.1968.tb09821.x. [DOI] [PubMed] [Google Scholar]
  16. Leszkovszky G., Tardos L. Some effects of propranolol on the central nervous system. J Pharm Pharmacol. 1965 Aug;17(8):518–519. doi: 10.1111/j.2042-7158.1965.tb07715.x. [DOI] [PubMed] [Google Scholar]
  17. Lilleheil G., Roed A. Antitetanic effect of propranolo on mammalian motor-nerve and skeletal muscle, and combined action of propranolol and neostigmine on the neuro-muscular transmission. Arch Int Pharmacodyn Ther. 1971 Nov;194(1):129–140. [PubMed] [Google Scholar]
  18. Mantegazza P., Naimzada K. M., Riva M. Effects of propranolol on some activities of amphetamine. Eur J Pharmacol. 1968 Aug;4(1):25–30. doi: 10.1016/0014-2999(68)90005-8. [DOI] [PubMed] [Google Scholar]
  19. Masuoka D., Hansson E. Autoradiographic distribution studies of adrenergic blocking agents. II. 14C-propranolol, a beta-receptor-type blocker. Acta Pharmacol Toxicol (Copenh) 1967;25(4):447–455. doi: 10.1111/j.1600-0773.1967.tb00413.x. [DOI] [PubMed] [Google Scholar]
  20. Murmann W., Almirante L., Saccani-Guelfi M. Central nervous system effects of four beta-adrenergic receptor blocking agents. J Pharm Pharmacol. 1966 May;18(5):317–318. doi: 10.1111/j.2042-7158.1966.tb07878.x. [DOI] [PubMed] [Google Scholar]
  21. Mylecharane E. J., Raper C. Further studies on the adrenergic neuron blocking activity of some -adrenoceptor antagonists and guanethidine. J Pharm Pharmacol. 1973 Mar;25(3):213–220. doi: 10.1111/j.2042-7158.1973.tb10627.x. [DOI] [PubMed] [Google Scholar]
  22. Mylecharane E. J., Raper C. Prejunctional actions of some beta-adrenoreceptor antagonists in the vas deferens preparation of the guinea-pig. Br J Pharmacol. 1970 May;39(1):128–138. doi: 10.1111/j.1476-5381.1970.tb09562.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nicholson A. N., Wright C. M., Ferres H. M. Impaired performance on delayed matching in monkeys by heptabarbitone, pentobarbitone sodium and quinalbarbitone sodium. Neuropharmacology. 1973 Apr;12(4):311–317. doi: 10.1016/0028-3908(73)90090-7. [DOI] [PubMed] [Google Scholar]
  24. Paradelis A. G., Theocharidis N. C., Logaras G. Effect of propranolol on the isolated phrenic nerve-diaphragm preparation of the rat. Arzneimittelforschung. 1973 Jan;23(1):38–40. [PubMed] [Google Scholar]
  25. Romero J. A., Zatz M., Kebabian J. W., Axelrod J. Circadian cycles in binding of 3H-alprenolol to beta-adrenergic receptor sites in rat pineal. Nature. 1975 Dec 4;258(5534):435–436. doi: 10.1038/258435a0. [DOI] [PubMed] [Google Scholar]
  26. Saelens D. A., Daniell H. B., Webb J. G. Studies on the interactions of propranolol with adrenergic neurons. J Pharmacol Exp Ther. 1977 Sep;202(3):635–645. [PubMed] [Google Scholar]
  27. Schechter Y., Weinstock M. Beta-adrenoceptor blocking agents and responses to adrenaline and 5-hydroxytryptamine in rat isolated stomach and uterus. Br J Pharmacol. 1974 Oct;52(2):283–287. doi: 10.1111/j.1476-5381.1974.tb09711.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schnelle K., Garrett E. R. Pharmacokinetics of the -adrenergic blocker sotalol in dogs. J Pharm Sci. 1973 Mar;62(3):362–375. doi: 10.1002/jps.2600620303. [DOI] [PubMed] [Google Scholar]
  29. Shah U. H., Jindal M. N., Patel V. K., Kelkar V. V. Central actions of some beta-adrenoceptor blocking agents. Arzneimittelforschung. 1974 Oct;24(10):1581–1584. [PubMed] [Google Scholar]
  30. Singh K. P., Bhandari D. S., Mahawar M. M. Effects of propranolol (a beta adrenergic blocking agent) on some central nervous system parameters. Indian J Med Res. 1971 May;59(5):786–794. [PubMed] [Google Scholar]
  31. Smith A., Hayashida K., Kim Y. Inhibition by propranolol of ethanol-induced narcosis. J Pharm Pharmacol. 1970 Aug;22(8):644–645. doi: 10.1111/j.2042-7158.1970.tb10595.x. [DOI] [PubMed] [Google Scholar]
  32. U'Prichard D. C., Synder S. H. Differential labelling of alpha and beta-noradrenergic receptors in calf cerebellum membranes with 3H-adrenaline. Nature. 1977 Nov 17;270(5634):261–263. doi: 10.1038/270261a0. [DOI] [PubMed] [Google Scholar]
  33. Usubiaga J. E. Neuromuscular effects of beta-adrenergic blockers and their interaction with skeletal muscle relaxants. Anesthesiology. 1968 May-Jun;29(3):484–492. doi: 10.1097/00000542-196805000-00021. [DOI] [PubMed] [Google Scholar]
  34. Weinstock M., Schechter Y. Antagonism by propranolol of the ganglion stimulant action of 5-hydroxytryptamine. Eur J Pharmacol. 1975 Jun-Jul;32(02):293–301. doi: 10.1016/0014-2999(75)90296-4. [DOI] [PubMed] [Google Scholar]
  35. Weinstock M., Speiser Z. Modification by propranolol and related compounds of motor activity and stereotype behaviour induced in the rat by amphetamine. Eur J Pharmacol. 1974 Jan;25(1):29–35. doi: 10.1016/0014-2999(74)90090-9. [DOI] [PubMed] [Google Scholar]
  36. Weinstock M., Weiss C., Gitter S. Blockade of 5-hydroxytryptamine receptors in the central nervous system by beta-adrenoceptor antagonists. Neuropharmacology. 1977 Apr;16(4):273–276. doi: 10.1016/0028-3908(77)90106-x. [DOI] [PubMed] [Google Scholar]
  37. Wislicki L. Excitatory and depressant effects of beta-adrenoceptor blocking agents on skeletal muscle. Arch Int Pharmacodyn Ther. 1969 Dec;182(2):310–317. [PubMed] [Google Scholar]

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

RESOURCES