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. 1985 Feb;48(2):101–106. doi: 10.1136/jnnp.48.2.101

The relationship between serum concentrations and central nervous system actions of metoprolol.

F M Gengo, J C Ermer, C Carey, G C Kalonaros, W B McHugh
PMCID: PMC1028207  PMID: 3981166

Abstract

The relationship between serum levels of metoprolol, hydroxymetoprolol and changes in psychomotor function as measured by standard reaction time and flash fusion frequency was studied. Blinded subjects were given placebo or 150 mg dose of metoprolol and crossed over on the next study day. Flash fusion frequency, reaction time, and serial blood levels of metoprolol and hydroxymetoprolol were collected. Oral dosing of metoprolol produced no significant changes in reaction time. However, significant decreases in flash fusion frequency were observed from 2 to 6 hours after the dose. Changes in flash fusion frequency were related to levels of metoprolol. Flash fusion frequency changes lagged behind the time course of metoprolol concentrations. The nadir of variance in the metoprolol plus hydroxymetoprolol concentration-effect relationship occurred when potency of hydroxymetoprolol was assumed to be 0.3 of metoprolol. These data suggest that the central nervous system actions of metoprolol are related to metoprolol serum levels and occur at low metoprolol concentrations. However, CNS effects of metoprolol do not intensify at high concentrations. Further CNS activity of hydroxymetoprolol may explain the lag seen in the relationship between concentration and CNS effect.

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Selected References

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  1. Atkinson A. J., Jr, Strong J. M. Effect of active drug metabolites on plasma level-response correlations. J Pharmacokinet Biopharm. 1977 Apr;5(2):95–109. doi: 10.1007/BF01066214. [DOI] [PubMed] [Google Scholar]
  2. Belpaire F. M., Bogaert M. G., Rosseneu M. Binding of beta-adrenoceptor blocking drugs to human serum albumin, to alpha 1-acid glycoprotein and to human serum. Eur J Clin Pharmacol. 1982;22(3):253–256. doi: 10.1007/BF00545224. [DOI] [PubMed] [Google Scholar]
  3. Caprani O., Sveinsdottir E., Lassen N. SHAM, a method for biexponential curve resolution using initial slope, height, area and moment of the experimental decay type curve. J Theor Biol. 1975 Aug;52(2):299–315. doi: 10.1016/0022-5193(75)90003-x. [DOI] [PubMed] [Google Scholar]
  4. Collste P., Borg K. O., Aström H., von Bahr C. Contribution of 4-hydroxy-alprenolol to adrenergic beta receptor blockade of alprenolol. Clin Pharmacol Ther. 1979 Apr;25(4):416–422. doi: 10.1002/cpt1979254416. [DOI] [PubMed] [Google Scholar]
  5. Greenblatt D. J., Koch-Weser J. Adverse reactions to beta-adrenergic receptor blocking drugs: a report from the Boston collaborative drug surveillance program. Drugs. 1974;7(1):118–129. doi: 10.2165/00003495-197407010-00008. [DOI] [PubMed] [Google Scholar]
  6. Johnson L. C., Chernik D. A. Sedative-hypnotics and human performance. Psychopharmacology (Berl) 1982;76(2):101–113. doi: 10.1007/BF00435262. [DOI] [PubMed] [Google Scholar]
  7. Koch-Weser J. Editorial: Non-beta-blocking actions of propranolol. N Engl J Med. 1975 Nov 6;293(19):988–990. doi: 10.1056/NEJM197511062931909. [DOI] [PubMed] [Google Scholar]
  8. Landauer A. A., Pocock D. A., Prott F. W. Effects of atenolol and propranolol on human performance and subjective feelings. Psychopharmacology (Berl) 1979 Jan 31;60(2):211–215. doi: 10.1007/BF00432296. [DOI] [PubMed] [Google Scholar]
  9. Levy G., Gibaldi M., Jusko W. J. Multicompartment pharmacokinetic models and pharmacologic effects. J Pharm Sci. 1969 Apr;58(4):422–424. doi: 10.1002/jps.2600580406. [DOI] [PubMed] [Google Scholar]
  10. Levy G. Kinetics of pharmacologic effects. Clin Pharmacol Ther. 1966 May-Jun;7(3):362–372. doi: 10.1002/cpt196673362. [DOI] [PubMed] [Google Scholar]
  11. Lyngstam O., Rydén L. Metoprolol and atenolol administered once daily in primary hypertension. A clinical comparison of the efficacy of two selective beta-adrenoceptor blocking agents. Acta Med Scand. 1981;209(4):261–266. [PubMed] [Google Scholar]
  12. Regårdh C. G., Ek L., Hoffmann K. J. Plasma levels and beta-blocking effect of alpha-hydroxymetoprolol--metabolite of metoprolol--in the dog. J Pharmacokinet Biopharm. 1979 Oct;7(5):471–479. doi: 10.1007/BF01062389. [DOI] [PubMed] [Google Scholar]
  13. SIMONSON E., BROZEK J. Flicker fusion frequency; background and applications. Physiol Rev. 1952 Jul;32(3):349–378. doi: 10.1152/physrev.1952.32.3.349. [DOI] [PubMed] [Google Scholar]
  14. Salem S. A., McDevitt D. G. Central effects of beta-adrenoceptor antagonists. Clin Pharmacol Ther. 1983 Jan;33(1):52–57. doi: 10.1038/clpt.1983.7. [DOI] [PubMed] [Google Scholar]
  15. Sheiner L. B., Stanski D. R., Vozeh S., Miller R. D., Ham J. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther. 1979 Mar;25(3):358–371. doi: 10.1002/cpt1979253358. [DOI] [PubMed] [Google Scholar]
  16. Trafford J. A., McGonigle R., Bowles J., O'Neal H., Bennet-Jones D. N., Halford L. A two year clinical evaluation of atenolol and metoprolol in the treatment of hypertension. Br J Clin Pract. 1982 Oct;36(10):350–352. [PubMed] [Google Scholar]

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