Effects of the anti-migraine drug sumatriptan on muscle energy metabolism: relationship to side-effects.
Sumatriptan succinate (Imitrex) is a 5-HT (5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5-20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.
Boska
M D
MD
Henry Ford Hospital NMR Research Laboratory, Henry Ford Health Sciences Center, Detroit, MI, USA. boskam@neurnis.neuro.hfh.edu
Welch
K M
KM
Schultz
L
L
Nelson
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D003402:Creatine Kinase / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism*; D020325:Migraine with Aura / Q000188:drug therapy / Q000378:metabolism; D020326:Migraine without Aura / Q000188:drug therapy / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D018170:Sumatriptan / Q000009:adverse effects / Q000627:therapeutic use*; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000627:therapeutic use*
D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D000255:Adenosine Triphosphate; D018170:Sumatriptan; D003402:Creatine Kinase