Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Oct 8;2008(4):CD004571.
doi: 10.1002/14651858.CD004571.pub2.

Calcium antagonists for Duchenne muscular dystrophy

Affiliations

Calcium antagonists for Duchenne muscular dystrophy

Margaret F Phillips et al. Cochrane Database Syst Rev. .

Abstract

Background: Duchenne muscular dystrophy (DMD) is a progressive muscle condition starting in childhood, leading to severe disability and a shortened life span. It is due to severe deficiency of the protein dystrophin which performs both structural and signalling roles within skeletal and cardiac myocytes. Calcium accumulates in dystrophic muscle cells and plays a role in cell damage. It has been hypothesised that use of calcium antagonists might reduce this calcium load and its toxic effect on muscle cells.

Objectives: To evaluate the effects of calcium antagonists on muscle function and muscle strength in people with DMD.

Search strategy: The Cochrane Neuromuscular Disease Group Trials Register (February 2008), MEDLINE (from January 1950 to March 2008) and EMBASE (from January 1947 to March 2008) were searched. Search terms were 'calcium antagonists' or 'calcium channel blocker' or 'dantrolene' or 'verapamil' or 'nifedipine' or 'flunarizine' or 'diltiazem' or 'amlodipine' or 'nicardipine' and 'Muscular Dystrophy, Duchenne'. Bibliographies in reports of any trials were also searched.

Selection criteria: All randomised or quasi-randomised controlled trials of any calcium antagonist in people with DMD.

Data collection and analysis: Both authors assessed all identified trials for inclusion in the study on the basis of whether they fulfilled the selection criteria. Both authors extracted data from the trials and assessed the methodological quality. Had there been more than one trial of the same intervention and outcome of sufficient methodological quality, we had planned to undertake a meta-analysis.

Main results: Five randomised or quasi-randomised double-blind trials fulfilled the selection criteria, but were not sufficiently comparable to undertake a meta-analysis. The drugs studied were verapamil (8 participants), diltiazem (56 participants), nifedipine (105 participants) and flunarizine (27 participants). There were limitations in the description of blinding and randomisation, and definition of outcome measures. One trial, using verapamil, showed a difference between groups in muscle force measured by ergometry, but also revealed cardiac side effects. The numbers of people included in the trials were low, and so the studies may not have included enough people for sufficient power to detect small differences in muscle force or function between placebo and control groups. In addition, calcium antagonists were in an early stage of development and some of the second generation drugs that have a better side effect profile, such as amlodipine, have not been studied.

Authors' conclusions: There is no evidence to show a significant beneficial effect of calcium antagonists on muscle function in DMD.

PubMed Disclaimer

Conflict of interest statement

None

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Update of

  • doi: 10.1002/14651858.CD004571

Similar articles

Cited by

References

References to studies included in this review

Dick 1986 {published data only}
    1. Dick D, Gardner‐Medwin D, Gates P, Gibson M, Simpson J, Walls T. A trial of flunarizine in the treatment of Duchenne Muscular Dystrophy. Muscle & Nerve 1986;9:349‐54. - PubMed
Emery 1983 {published data only}
    1. Emery A, Skinner R. Double blind controlled trial of a calcium blocker in Duchenne Muscular Dystrophy. Cardiomyology 1983;2:13‐23.
    1. Emery AEH, Skinner R, Howden LC, Matthews MB. Verapamil in Duchenne muscular dystrophy. Lancet 1982;319(8271):559. - PubMed
Moxley 1987 {published data only}
    1. Moxley RT, Brooke MH, Fenichel GM, Mendell J, Griggs R, Miller P, et al. Clinical investigation in Duchenne dystrophy. VI Double blind controlled trial of nifedipine. Muscle & Nerve 1987;10(1):22‐33. - PubMed
Pernice 1988 {published data only}
    1. Pernice W, Beckmann R, Ketelsen U‐P, Frey M, Schmidt‐Redemann B, Haap KP, et al. A double blind placebo controlled trial of diltiazem in Duchenne dystrophy. Klinische Wochenschrift 1988;66(13):565‐70. - PubMed
Toifl 1991 {published data only}
    1. Toifl K, Presterl E, Graninger W. Lack of effect of diltiazem in the treatment of Duchenne's muscular dystrophy: a double blind placebo controlled study [Fehlende Wirksamkeit von Diltiazem bei Duchenne‐Muskeldystrophie: eine placebo‐kontrollierte Doppelblindstudie]. Wiener klinische Wochenschrift 1991;103(8):232‐5. - PubMed

References to studies excluded from this review

Bertorini 1988 {published data only}
    1. Bertorini TE, Palmieri GMA, Griffin JW, Igarishi M, McGee J, Brown R, et al. Effect of chronic treatment with calcium antagonist diltiazem in Duchenne muscular dystrophy. Neurology 1988;38(4):609‐13. - PubMed
Bertorini 1991 {published data only}
    1. Bertorini TE, Palmieri GMA, Griffin J, Igarishi M, Hinton A, Karas JG. Effect of dantrolene in Duchenne muscular dystrophy. Muscle & Nerve 1991;14(6):503‐7. - PubMed
Garcia 1990 {published data only}
    1. Garcia AM, Goldemberg AL, Fernandez H, Fortunato M, Ricci L, Trucco RE. Effect of chronic administration of verapamil in Duchenne muscular dystrophy. General Pharmacology 1990;21(6):939‐42. - PubMed

Additional references

Anand 1980
    1. Anand R, Emery AE. Calcium‐stimulated enzyme efflux from human skeletal muscle. Research communications in chemical pathology and pharmacology 1980;28(3):541‐50. - PubMed
Archibald 1959
    1. Archibald KC, Vignos PJ. A study of contractures in muscular dystrophy. Archives of Physical Medicine 1959;40(4):150‐7. - PubMed
Biggar 2006
    1. Biggar WD, Harris VA, Eliasoph L, Alman B. Long‐term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscular Disorders 2006;16:249‐55. - PubMed
Bodensteiner 1978
    1. Bodensteiner JB, Engel AG. Intracellular calcium accumulation in Duchenne dystrophy and other myopathies. Neurology 1978;28(5):439‐46. - PubMed
Bonilla 1988
    1. Bonilla E, Samitt CE, Miranda AF, Hays AP, Salviati G, DiMauro S, et al. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 1988;54(4):447‐52. - PubMed
Brooke 1981
    1. Brooke MH, Griggs RC, Mendell JR, Fenichel GM, Shumate JB, Pellegrino RJ. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle & Nerve 1981;4(3):186‐97. - PubMed
Chang 1988
    1. Chang CC, Lin SO, Hong SJ, Chiou LC. Neuromuscular block by verapamil and diltiazem and inhibition of acetylcholine release. Brain Research 1988;454(1‐2):332‐9. - PubMed
Cohn 2001
    1. Cohn RD, Durbeej M, Moore SA, Coral‐Vazquez R, Prouty S, Campbell KP. Prevention of cardiomyopathy in mouse models lacking the sarcoglycan‐sarcospan complex. The Journal of Clinical Investigation 2001;107(2):153‐4. - PMC - PubMed
Cornelio 1984
    1. Cornelio F, Dworzak F, Morandi L. Therapeutic trials in Duchenne Muscular Dystrophy. Italian Journal of Neurological Sciences 1984;S3:133‐6. - PubMed
Cullen 1975
    1. Cullen MJ, Fulthorpe JJ. Stages in fibre breakdown in Duchenne muscular dystrophy: an electron‐microscopic study. Journal of the Neurological Sciences 1975;24(2):179‐200. - PubMed
Danialou 2001
    1. Danialou G, Comtois AS, Dudley R, Karpati G, Vincent G, Rosiers C, et al. Dystrophin deficient cardiomyocytes are abnormally vulnerable to mechanical stress‐induced contractile failure and injury. FASEB Journal 2001;15(9):1655‐7. - PubMed
Eagle 2002
    1. Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscular Disorders 2002;12(10):926‐9. - PubMed
Elsheikh 2007
    1. Elsheikh BH, Bollman E, Peruggia M, King W, Galloway G, Kissel JT. Pilot trial of diltiazem in facioscapulohumeral muscular dystrophy. Neurology 2007;68(17):1428‐9. - PubMed
Figulla 1996
    1. Figulla HR, Gietzen F, Zeymer U, Raiber M, Hegselmann J, Soballa R, et al. Diltiazem improves cardiac function and exercise capacity in patients with idiopathic dilated cardiomyopathy. Results of the diltiazem in dilated cardiomyopathy trial. Circulation 1996;94(3):346‐52. - PubMed
Fong 1990
    1. Fong PY, Turner PR, Denetclaw WF, Steinhardt RA. Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin. Science 1990;250(4981):673‐6. - PubMed
Gilroy 1963
    1. Gilroy J, Cahalan JL, Berman R, Newman M. Cardiac and pulmonary complications in Duchenne's progressive muscular dystrophy. Circulation 1963;27(4 Pt 1):484‐93. - PubMed
Hernandez 1999
    1. Hernandez‐Hernandez R. Effects of amlodipine and enelapril on platelet function in patients with mild to moderate hypertension. International journal of clinical pharmacology and therapeutics 1999;37(7):323‐31. - PubMed
Higgins 2008
    1. Higgins JPT, Altman DG (editors). Chapter 8: Assessing risk of bias in included studies. Higgins JPT, Green S (editors) Cochrane Handbook for Systematic Reviews of Interventions. Chichester (UK): John Wiley & Sons, 2008.
Hudecki 1984
    1. Hudecki MS, Pollina CM, Heffner RR. In vivo effects of three calcium blockers on chickens with inherited muscular dystrophy. Experimental Neurology 1984;84(3):512‐23. - PubMed
Ibraghimov 1992
    1. Ibraghimov‐Beskrovnaya O, Ervasti JM, Leveille CJ, Slaughter CA, Sernett SW, Campbell KP. Primary structure of dystrophin‐associated glycoproteins linking dystrophin to the extracellular matrix. Nature 1992;355(6362):696‐702. - PubMed
Iwata 2003
    1. Iwata Y, Katanosaka y, Arai Y, Komamura K, Miyatake K, Shigekawa M. A novel mechanism of myocyte degeneration involving the Ca2+‐permeable growth factor regulated channel. Journal of Cell Biology 2003;161(5):957‐67. - PMC - PubMed
Jackson 1991
    1. Jackson MJ, McArdle A, Edwards RHT. Free radicals, calcium and damage in dystrophic and normal skeletal muscle. In Calcium free radicals and tissue damage. Cambridge: Cambridge University Press, 1991:pp139‐48..
Johnson 1993
    1. Johnson PL, Bhattacharya SK. Regulation of membrane‐mediated chronic muscle degeneration in dystrophic hamsters by calcium channel blockers: diltiazem, nifedipine and verapamil. Journal of the Neurological Sciences 1993;115(1):76‐90. - PubMed
Jones 1984
    1. Jones DA, Jackson MJ, McPhail G, Edwards RHT. Experimental mouse muscle damage: the importance of external calcium. Clinical Science 1984;66(3):317‐22. - PubMed
Koenig 1987
    1. Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987;50(3):509‐17. - PubMed
Kumar 2004
    1. Kumar A, Khandelwal N, Malya R, Reid MB. Loss of dystrophin causes aberrant mechanotransduction in skeletal muscle fibres. The FASEB journal 2004;18(1):102‐13. - PubMed
Mallouk 2000
    1. Mallouk N, Jacquemond V, Allard B. Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibres detected with Ca2+ activated K+ channels. Proceedings of the National Academy of Sciences of the United States of America 2000;97(9):4950‐5. - PMC - PubMed
Manzur 2008
    1. Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858] - DOI - PubMed
Mariol 2001
    1. Mariol M‐C, Segalat L. Muscular degeneration in the absence of dystrophin is a calcium‐dependent process. Current biology 2001;11(21):1691‐4. - PubMed
Markham 2008
    1. Markham LW, Kinnett K, Wong BL, Woodrow Benson D, Cripe L. Corticosteroid treatment retards development of ventricular dysfunction in Duchenne muscular dystrophy. Neuromuscular Disorders 2008;18:365‐70. - PubMed
Mason 1999
    1. Mason RP, Walter MF, Trumbore MW, Olmstead EG jr, Mason PE. Membrane antioxidant effects of the charged dihydropyridine calcium antagonist amlodipine. Journal of molecular and cellular cardiology 1999;31(1):275‐81. - PubMed
Melacini 1986
    1. Melacini P, Fasoli G, Mammola C, Angelini C, Dalla Volta S. Cardiac complications during a trial with a calcium antagonist in a boy with Duchenne muscular dystrophy. Cardiomyology 1986;5(1):39‐47.
Miyatake 1989
    1. Miyatake M, Miike T, Zhao JE, Yoshioka K, Uchino M, Tuki G. Possible systemic smooth muscle layer dysfunction due to a deficiency of dystrophin in Duchenne muscular dystrophy. Journal of the Neurological Sciences 1989;93(1):11‐17. - PubMed
Moens 1993
    1. Moens P, Baatsen PH, Marechal G. Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch. Journal of Muscle Research and Cell motility 1993;14(4):446‐51. - PubMed
Mohamed 2000
    1. Mohamed K, Appleton R, Nicolaides P. Delayed diagnosis of Duchenne muscular dystrophy. European Journal of Paediatric Neurology 2000;4(5):219‐23. - PubMed
MRC 1976
    1. Medical Research Council. Aids to the investigation of peripheral nerve injuries. London: HMSO, 1976.
Neglia 2000
    1. Neglia D, Sambuceti G, Giorgetti A, Bartoli M, Salvadori P, Sorace O, et al. Effects of long‐term treatment with verapamil on left ventricular function and myocardial bloodflow in patients with dilated cardiomyopathy without overt heart failure. Journal of Cardiovascular Pharmacology 2000;36(6):744‐50. - PubMed
Nigro 1990
    1. Nigro G, Comi LI, Politano L, Bain RJ. The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. International Journal of Cardiology 1990;26(3):271‐7. - PubMed
O'Connor 1999
    1. O'Connor CM, Radensky PW, Unger AN, Martin BC. Hospital use and costs among patients with nonischemic cardiomyopathy in the first prospective randomized amlodipine survival evaluation study. Clinical Therapeutics 1999;21(7):1254‐65. - PubMed
Oberc 1977
    1. Oberc MA, Engel WK. Ultrastructural localization of calcium in normal and abnormal skeletal muscle. Laboratory Investigation 1977;36(6):566‐77. - PubMed
Ozkul 2007
    1. Ozkul Y. Influence of calcium channel blocking drugs in neuromuscular transmission. Clinical Neurophysiology 2007;118(9):2005‐8. - PubMed
Packer 1996
    1. Packer M, O'Connor CM, Ghali JK, Pressler ML, Carson PE, Belkin RN, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. New England Journal of Medicine 1996;335(15):1107‐14. - PubMed
Petrof 1993
    1. Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL. Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proceedings of the National Academy of Sciences of the USA 1993;90(8):3710‐14. - PMC - PubMed
Porter 2002
    1. Porter GA, Makuck RF, Rivkees SA. Reduction in intracellular calcium levels inhibits myoblast differentiation. Journal of Biological Chemistry 2002;277(32):28942‐7. - PubMed
Rideau 1983
    1. Rideau Y. Prolongation of life in Duchenne's muscular dystrophy. Acta Neurologica 1983;5(2):118‐24. - PubMed
Roed 1991
    1. Roed A. Selective potentiation of subtetanic and tetanic contractions by the calcium‐channel antagonist nifedipine in the rat diaphragm preparation. General Pharmacology 1991;22(2):313‐18. - PubMed
Schulz 2002
    1. Schulz KF, Grimes DA. Allocation concealment in randomised trials: defending against deciphering. Lancet 2002;359(9306):614‐8. - PubMed
Scott 1982
    1. Scott OM, Hyde SA, Goddard C, Dubowitz V. Quantitation of muscle function in children: a prospective study in Duchenne muscular dystrophy. Muscle & Nerve 1982;5(4):291‐301. - PubMed
Sun 1995
    1. Sun J, Triggle DJ. Calcium channel antagonists: cardiovascular selectivity of action. Journal of pharmacology and experimental therapeutics 1995;274(1):419‐26. - PubMed
Turner 1991
    1. Turner PR, Fong PY, Denetclaw WF, Steinhardt RA. Increased calcium influx in dystrophic muscle. Journal of Cell Biology 1991;115(6):1701‐12. - PMC - PubMed
Turturro 2005
    1. Turturro F, Rocca B, Gumina S, Cristofaro R, Mangiola F, Maggiano N, et al. Impaired primary hemostasis with normal platelet function in Duchenne muscular dystrophy during highly‐invasive spinal surgery. Neuromuscular Disorders 2005;15(8):532‐40. - PubMed
Van Essen 1997
    1. Essen AJ, Verhij JBGM, Reefhuis J, Fidler V, Begeer JH, Visser M, et al. The natural history of Duchenne muscular dystrophy. Analysis of data from Dutch survey and review of age related events [PhD thesis]. Vol. Chapter 3, 1997:49‐68. [ISBN 90 367 0711]
Vandebrouck 2002
    1. Vanderbrouck C, Martin D, Colson‐Van Schoor M, Debaix H, Gailly P. Involvement of TRPC in the abnormal calcium influx observed in dystrophic (mdx) mouse skeletal muscle fibers. Journal of Cell Biology 2002;158(6):1089‐96. - PMC - PubMed
Wijeysundera 2003
    1. Wijeysundera HC, Hansen MS, Stanton E, Cropp AS, Hall C, Dhalla NS, et al. Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine. American Heart Journal 2003;146(2):291‐7. - PubMed
Zalman 1983
    1. Zalman F, Perloff JK, Durant NN, Campion DS. Acute respiratory failure following intravenous verapamil in Duchenne's muscular dystrophy. American Heart Journal 1983;105(3):510‐11. - PubMed
Zubrzycka‐Gaarn 1988
    1. Zubrzycka‐Gaarn EE, Bulman DE, Karpati G, Burghes AH, Belfall B, Klamut HJ, et al. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle. Nature 1988;333(6172):466‐9. - PubMed

Publication types

MeSH terms

LinkOut - more resources