Mechanism of Action

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Triptans are specifically designed to bind to the 5-HT1B/1D receptors based on the findings that 5-HT1B receptors are present in the cranial blood vessels279,280 and 5-HT1B/1D receptors are found in the trigeminal pain pathway.280,281 Three distinct mechanisms have been suggested to explain the actions of triptans: (a) Triptans abort migraine headache by its agonist action at the 5-HT1B receptors, thereby inducing vasoconstriction of the meningeal, dural, or pial blood vessels.279 (b) Triptans also inhibit neurogenic inflammation via its presynaptic stimulation of 5-HT1D receptors and/or through its additional action at the 5-HT1B/1D receptors.281 (c) Triptans relieve migraine pain transmission most likely because of its inhibitory action at the trigeminal pain pathway mediated via 5-

HT receptors.259,279,280

HT1B/1D/1F receptors.

Antimigraine Drugs Acting on 5-HT|B/1D Receptors


Sumatriptan was the first triptan approved (1991) for the acute treatment of migraine headaches. It has the lowest oral bioavailability among all triptans because of its low lipophilicity. The availability of many different dosage forms (i.e., an oral tablet, a SC injection, a nasal spray formulation, and a suppository) allows the flexibility of tailoring therapy to the needs of the individual patients, thus making sumatriptans a very useful drug for an acute treatment of migraine headaches.262,282 It also has a very fast onset of action via SC injection or nasal spray administration. However, sumatriptan is contraindicated with monoamine oxidase inhibitors because it is primarily degraded by hepatic MAO-A. Thus, it may require frequent dosing as a result of its short duration of action to prevent migraine recurrence.262,282


Zolmitriptan, the second triptan marketed (approved in 1997), has a much better bioavailability (40%-48%) than sumatriptan. It is rapidly absorbed after oral or nasal spray administration. It also has an orally disintegrating tablet formulation (Zomig ZMT), which can be taken without water. Zolmitriptan undergoes rapid N-demethylation via CYP1A2 to a more potent, active metabolite, N-desmethylzolmitrip-tan, which is 2 to 6 times more potent than the parent drug.262,283 This active metabolite was detected 5 minutes after dosing and accounts for about two thirds of the plasma concentration of the administered dose of the parent drug.284 Thus, it is reasonable to assume that the therapeutic effects and especially the CNS side effects of zolmitriptan must be in part attributed to the plasma levels of this active metabolite, at least until it is further degraded by hepatic MAO-A to its inactive indole acetic acid derivatives.262,283


Naratriptan, the third triptan approved in 1998, is one of the most lipophilic triptans marketed to date. It has a much improved bioavailability (63% in men and 74% in women), a greater affinity for 5-HT1B/1D receptors (3-6 times), and a lower recurrence rate than sumatriptan because of its much longer elimination half-life.262,285 Naratritan also has a favorable CNS side effect profile when compared with suma-triptan or zolmitriptan because of its metabolic stability, thereby lacking a N-demethylated active metabolite and a significant renal excretion (>70% of naratriptan is excreted unchanged and the rest of the administered dose is degraded via several CYP isozymes).262,270,286


Rizatriptan, approved in 1998, is a fast-acting triptan because of its moderate lipophilicity yet has a very short elimination half-life similar to sumatriptan (i.e., like suma-triptan, it is mainly metabolized by MAO-A). The only advantages of this drug when compared with sumatriptan are that it has a slightly faster onset and that it has an orally disintegrating tablet formulation which can be taken with-

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Headache Happiness

Headache Happiness

Headache Happiness! Stop Your Headache BEFORE IT STARTS. How To Get Rid Of Your Headache BEFORE It Starts! The pain can be AGONIZING Headaches can stop you from doing all the things you love. Seeing friends, playing with the kids... even trying to watch your favorite television shows. And just think of how unwelcome headaches are while you're trying to work.

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