Low dose Formoterol administration improves muscle function in dystrophic mdx mi

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Neuromuscul Disord. 2006 Nov 27

Low dose formoterol administration improves muscle function in

dystrophic mdx mice without increasing fatigue.

Harcourt LJ, Schertzer JD, Ryall JG, Lynch GS.

Basic and Clinical Myology Laboratory, Department of Physiology, The

University of Melbourne, 3010, Australia.

The beta(2)-adrenoceptor agonist (beta(2)-agonist), formoterol, has

been shown to cause muscle hypertrophy in rats even when

administered at the micromolar dose of 25mug/kg/day. We investigated

whether a similar low dose of formoterol could improve muscle

function in the dystrophic mdx mouse. Ten-week-old male mdx and wild-

type (C57BL/10) mice were administered formoterol (25mug/kg/day,

i.p.) for 4 weeks. Formoterol treatment increased extensor digitorum

longus (EDL) and soleus muscle mass, increased median muscle fibre

size in diaphragm, EDL, and soleus muscles, and increased maximum

force producing capacity in skeletal muscles of both wild-type and

mdx mice.

In contrast to other studies where beta(2)-agonists have been

administered to mice and rats, generally at higher doses, low dose

formoterol treatment did not increase the fatiguability of EDL,

soleus or diaphragm muscles. Although others have found formoterol

can decrease ubiquitin mRNA and proteasome activity when

administered to tumour bearing rats at high doses (2mg/kg/day), in

the present study low dose formoterol treatment did not alter

ubiquitin or the E1 and E3 ubiquitin ligases in diaphragm muscles of

wild-type or mdx mice, but it did reduce the level of ubiquitinated

proteins in diaphragm of wild-type mice.

The findings indicate that formoterol has considerably more powerful

anabolic effects on skeletal muscle than older generation beta(2)-

agonists (like clenbuterol and albuterol), and has considerable

therapeutic potential for muscular dystrophies and other

neuromuscular disorders where muscle wasting is indicated.