| Indication |
For the acute treatment of adult migraine with or without auras. |
| Pharmacodynamics |
Zolmitriptan is a selective agonist of serotonin
(5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally
and pharmacologically related to other selective 5-HT1B/1D receptor
agonists, and has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4
receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic,
dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This
action in humans correlates with the relief of migraine headache. In
addition to causing vasoconstriction, experimental data from animal
studies show that Zolmitriptan also activates 5-HT1 receptors
on peripheral terminals of the trigeminal nerve innervating cranial
blood vessels, which may also contribute to the antimigrainous effect of
Zolmitriptan in humans. |
| Mechanism of action |
Zolmitriptan binds with high affinity to human 5-HT1B and 5-HT1D
receptors leading to cranial blood vessel constriction. Current
theories proposed to explain the etiology of migraine headache suggest
that symptoms are due to local cranial vasodilatation and/or to the
release of sensory neuropeptides (vasoactive intestinal peptide,
substance P and calcitonin gene-related peptide) through nerve endings
in the trigeminal system. The therapeutic activity of zolmitriptan for
the treatment of migraine headache can most likely be attributed to the
agonist effects at the 5HT1B/1D receptors on intracranial blood vessels
(including the arterio-venous anastomoses) and sensory nerves of the
trigeminal system which result in cranial vessel constriction and
inhibition of pro-inflammatory neuropeptide release. |
| Absorption |
Mean absolute oral bioavailability is approximately 40%. Food has no affect on the rate and extent of absorption. |
| Volume of distribution |
|
| Protein binding |
25% |
| Metabolism |
Hepatic. There have been three metabolites identified: indole
acetic acid, N -oxide, and N-desmethyl metabolites. However, the
N-desmethyl is the only active metabolite. |
| Route of elimination |
Not Available |
| Half life |
The mean elimination half-life of zolmitriptan and of the active N-desmethyl metabolite is 3 hours. |
| Clearance |
|
| Toxicity |
Not Available |
