| Indication |
For treatment of acute migraine attacks with or without aura. |
| Pharmacodynamics |
Rizatriptan 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 Rizatriptan 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
Rizatriptan in humans. |
| Mechanism of action |
Three distinct pharmacological actions have been implicated in the
antimigraine effect of the triptans: (1) stimulation of presynaptic
5-HT1D receptors, which serves to inhibit both dural vasodilation and
inflammation; (2) direct inhibition of trigeminal nuclei cell
excitability via 5-HT1B/1D receptor agonism in the brainstem and (3)
vasoconstriction of meningeal, dural, cerebral or pial vessels as a
result of vascular 5-HT1B receptor agonism. |
| Absorption |
Rapid following oral administration. Bioavailability is 45%. Food
has no effect on the bioavailability of rizatriptan. However,
administering rizatriptan with food will delay by 1 hour the time to
reach peak plasma concentration. The rate of absorption is not affected
by the presence of a migraine attack. |
| Volume of distribution |
- 140 L [male]
- 110 L [female]
|
| Protein binding |
14% |
| Metabolism |
Rizatriptan is metabolized by monoamine oxidase A isoenzyme
(MAO-A) to an inactive indole acetic acid metabolite. In addition,
several other inactive metabolites are formed. An active metabolite,
N-monodesmethyl-rizatriptan, with pharmacological activity similar to
that of the parent compound has been identified in small concentrations
(14%) in the plasma. |
| Route of elimination |
Approximately 14% of an oral dose is excreted in urine as
unchanged rizatriptan while 51% is excreted as indole acetic acid
metabolite, indicating substantial first pass metabolism. |
| Half life |
2-3 hours |
| Clearance |
Not Available |
| Toxicity |
Symptoms of overdose include dizziness, fainting, heart and blood
vessel problems, high blood pressure, loss of bowel and bladder control,
slow heartbeat, and vomiting. |
