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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1990 Nov;30(5):665–672. doi: 10.1111/j.1365-2125.1990.tb03834.x

Selective beta-adrenoceptor partial agonist effects of pindolol and xamoterol on skeletal muscle assessed by plasma creatine kinase changes in healthy subjects.

B Tomlinson 1, J M Cruickshank 1, Y Hayes 1, J C Renondin 1, J B Lui 1, B R Graham 1, A Jones 1, A D Lewis 1, B N Prichard 1
PMCID: PMC1368165  PMID: 1980200

Abstract

1. The effects of selective beta-adrenoceptor partial agonist activity on plasma creatine kinase (CK) and skeletal muscle symptoms were studied in normal volunteers. 2. A drug with beta 1-selective partial agonist activity (xamoterol) and one with partial agonist activity acting mainly through beta 2-adrenoceptors (pindolol) were each given for 3 weeks in a randomised double-blind crossover study in 10 subjects. Five additional subjects received only one drug. Plasma CK levels were monitored during a baseline placebo run-in phase, the active treatment period and a placebo washout phase which continued until CK levels returned to baseline. 3. The degree of beta-adrenoceptor antagonism was determined by the inhibition of exercise-induced tachycardia and was similar for the two drug doses used. 4. During pindolol administration plasma CK levels rose compared with pretreatment baseline levels and with levels during xamoterol administration which did not rise. After pindolol was withdrawn CK levels reached higher peaks in some subjects after 1-5 days. 5. Muscle cramps were reported by five subjects during pindolol administration and by one of these subjects but to a lesser extent during xamoterol administration. 6. Pindolol may produce this effect, which was not seen with xamoterol, because of its specific beta 2-adrenoceptor partial agonist activity. Elevations in plasma CK produced by this type of drug or its withdrawal may cause confusion in the diagnosis of muscle disease or myocardial infarction unless the myocardial isoenzyme is measured.

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Selected References

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  1. Aellig W. H., Clark B. J. Is the ISA of pindolol beta 2-adrenoceptor selective? Br J Clin Pharmacol. 1987;24 (Suppl 1):21S–28S. doi: 10.1111/j.1365-2125.1987.tb03264.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Byrnes W. C., Clarkson P. M., White J. S., Hsieh S. S., Frykman P. N., Maughan R. J. Delayed onset muscle soreness following repeated bouts of downhill running. J Appl Physiol (1985) 1985 Sep;59(3):710–715. doi: 10.1152/jappl.1985.59.3.710. [DOI] [PubMed] [Google Scholar]
  3. Clarkson P. M., Ebbeling C. Investigation of serum creatine kinase variability after muscle-damaging exercise. Clin Sci (Lond) 1988 Sep;75(3):257–261. doi: 10.1042/cs0750257. [DOI] [PubMed] [Google Scholar]
  4. Cooper R. G., Stokes M. J., Edwards R. H., Stark R. D. Absence of excess peripheral muscle fatigue during beta-adrenoceptor blockade. Br J Clin Pharmacol. 1988 Apr;25(4):405–415. doi: 10.1111/j.1365-2125.1988.tb03323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Elfellah M. S., Dalling R., Kantola I. M., Reid J. L. Beta-adrenoceptors and human skeletal muscle characterisation of receptor subtype and effect of age. Br J Clin Pharmacol. 1989 Jan;27(1):31–38. doi: 10.1111/j.1365-2125.1989.tb05332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Forfar J. C., Brown G. J., Cull R. E. Proximal myopathy during beta-blockade. Br Med J. 1979 Nov 24;2(6201):1331–1332. doi: 10.1136/bmj.2.6201.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gill J. S., Beevers D. G. Bucindolol: effects on blood pressure, airways resistance and serum creatine phosphokinase. Eur J Clin Pharmacol. 1984;27(3):265–268. doi: 10.1007/BF00542157. [DOI] [PubMed] [Google Scholar]
  8. Gonasun L. M., Langrall H. Adverse reactions to pindolol administration. Am Heart J. 1982 Aug;104(2 Pt 2):482–486. [PubMed] [Google Scholar]
  9. Hollenberg N. K. Angiotensin converting enzyme inhibition and the kidney. Curr Opin Cardiol. 1988;3(Suppl 1):S19–S29. doi: 10.1097/00001573-198801001-00003. [DOI] [PubMed] [Google Scholar]
  10. Imataka K., Seki A., Takahashi N., Fujii J., Ohuchi Y., Kuwako K., Umeda T., Machii K., Hasegawa T., Ozoe A. [Elevation of serum creatine phosphokinase during pindolol treatment (author's transl)]. Nihon Naika Gakkai Zasshi. 1981 Apr 10;70(4):580–585. [PubMed] [Google Scholar]
  11. Jones D. A., Newham D. J., Round J. M., Tolfree S. E. Experimental human muscle damage: morphological changes in relation to other indices of damage. J Physiol. 1986 Jun;375:435–448. doi: 10.1113/jphysiol.1986.sp016126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LaPorta M. A., Linde H. W., Bruce D. L., Fitzsimons E. J. Elevation of creatine phosphokinase in young men after recreational exercise. JAMA. 1978 Jun 23;239(25):2685–2686. doi: 10.1001/jama.239.25.2685. [DOI] [PubMed] [Google Scholar]
  13. Liggett S. B., Shah S. D., Cryer P. E. Characterization of beta-adrenergic receptors of human skeletal muscle obtained by needle biopsy. Am J Physiol. 1988 Jun;254(6 Pt 1):E795–E798. doi: 10.1152/ajpendo.1988.254.6.E795. [DOI] [PubMed] [Google Scholar]
  14. Newham D. J., Jones D. A., Clarkson P. M. Repeated high-force eccentric exercise: effects on muscle pain and damage. J Appl Physiol (1985) 1987 Oct;63(4):1381–1386. doi: 10.1152/jappl.1987.63.4.1381. [DOI] [PubMed] [Google Scholar]
  15. Newham D. J., Jones D. A., Edwards R. H. Plasma creatine kinase changes after eccentric and concentric contractions. Muscle Nerve. 1986 Jan;9(1):59–63. doi: 10.1002/mus.880090109. [DOI] [PubMed] [Google Scholar]
  16. Nuttall A., Snow H. M. The cardiovascular effects of ICI 118,587: A beta 1-adrenoceptor partial agonist. Br J Pharmacol. 1982 Oct;77(2):381–388. doi: 10.1111/j.1476-5381.1982.tb09309.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Palmer K. N. Muscle cramp and oral salbutamol. Br Med J. 1978 Sep 16;2(6140):833–833. doi: 10.1136/bmj.2.6140.833-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rutherford O. M., Jones D. A., Newham D. J. Clinical and experimental application of the percutaneous twitch superimposition technique for the study of human muscle activation. J Neurol Neurosurg Psychiatry. 1986 Nov;49(11):1288–1291. doi: 10.1136/jnnp.49.11.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saruta T., Suzuki H., Kawamura M., Itoh H. Serum creatine phosphokinase levels during treatment with beta-adrenoreceptor blocking agents. J Cardiovasc Pharmacol. 1985 Jul-Aug;7(4):805–808. doi: 10.1097/00005344-198507000-00028. [DOI] [PubMed] [Google Scholar]
  20. Teicher A., Rosenthal T., Kissin E., Sarova I. Labetalol-induced toxic myopathy. Br Med J (Clin Res Ed) 1981 Jun 6;282(6279):1824–1825. doi: 10.1136/bmj.282.6279.1824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Toyama S., Suzuki K. [Effect of beta receptor blockader administration on the serum CPK level]. Nihon Rinsho. 1982;40(9):2112–2118. [PubMed] [Google Scholar]

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