| Indication |
For the treatment of migraine attacks with or without aura. |
| Pharmacodynamics |
Sumatriptan, an antimigraine drug, is a selective agonist of
vascular serotonin ((5-hydroxytryptamine; 5-HT) type 1-like receptors,
likely the 5-HT1D and 5-HT1B subtypes. It has no
significant affinity (as measured using standard radioligand binding
assays) or pharmacological activity at 5-HT2, 5-HT3 receptor subtypes or
at alpha1-, alpha2-, or beta-adrenergic; dopamine1; dopamine2;
muscarinic; or benzodiazepine receptors. |
| Mechanism of action |
The 5-HT1B and 5-HT1D receptors function as
autoreceptors, which inhibit the firing of serotonin neurons and a
reduction in the synthesis and release of serotonin upon activation.
After sumatriptan binds to these receptors, adenylate cyclase activity
is inhibited via regulatory G proteins, incrases intracellular calcium,
and affects other intracellular events. This results in vasoconstriction
and inhibtion of sensory nociceptive (trigeminal) nerve firing and
vasoactive neuropeptide release. |
| Absorption |
Approximately 15% |
| Volume of distribution |
- 2.7 L/kg [subcutaneous dosing]
|
| Protein binding |
14%-21% |
| Metabolism |
Hepatic. In vitro studies with human microsomes suggest that
sumatriptan is metabolized by monoamine oxidase (MAO), predominantly the
A isoenzyme. |
| Route of elimination |
Only 3% of the dose is excreted in the urine as unchanged
sumatriptan; 42% of the dose is excreted as the major metabolite, the
indole acetic acid analogue of sumatriptan. |
| Half life |
2.5 hours |
| Clearance |
- 1200 mL/min [Following a 6-mg SC injection]
|
| Toxicity |
Symptoms of overdose include convulsions, tremor, paralysis,
inactivity, ptosis, erythema of the extremities, abnormal respiration,
cyanosis, ataxia, mydriasis, salivation, and lacrimation. |
