Almotriptan

Migraine is a common condition characterized by severe headaches and accompanied by chronic head pain, nausea, vomiting, and photophobia. Migraines affect approximately 18% of women and 6% of men in the U.S. Migraines can significantly affect a person’s quality of life. Approximately 86% of women and 82% of men report some disability with each migraine attack. The loss of productivity associated with migraines is estimated to range from 6.5 to 17.2 billion dollars per year, making this condition a costly public health problem. Therefore, appropriate drug therapy is key to the treatment of this chronic condition.

Although the exact mechanism of migraines is still unknown, they are thought to be mediated by alterations in the activity, 5-hydroxytryptamine (5-HT). Of the seven classes of 5-HT receptors, the 5-HT1 receptor plays a key role in the pathogenesis of migraine. During a migraine attack, there are several neurological changes that take place, including neurogenic inflammation, activation of neuropeptides, and vasodilation of the meningeal vessels. The neurological changes result in the release of vasoactive neuropep-tides leading to vasodilation and producing the pain of a migraine. The 5-HT1B and 5-HT1D receptors are two of the five 5-HT1 subtypes identified and are thought to be directly involved in the origin of migraines. The 5-HT1B receptors are predominately located in the meningeal arteries and cause vasoconstriction of cranial vessels when stimulated, whereas the 5-HT1D receptors, found on trigeminal nerve endings, directly inhibit the release of the proinflam-matory neuropeptides when stimulated. There are currently six selective 5-HT1B/1D agonists available in the U.S. and one, eletriptan (Relpax, Pfizer) currently awaiting FDA approval (Table 1).

Table 1 Available 5-HT|B/|D Agonists

Price
5-ht!b/!d Agonist Dosage Form (number of tablets)
  5-, 20-mg nasal spray $118.08(6), $120.60(6)
(GlaxoSmithKline) 6 mg/0.5 ml sc injection $242.43 (5 vials)
25 mg $137.65(9)
50 mg, 100 mg $134.70(9)
Zolmitriptan (Zomig, AstraZeneca) 2.5 mg $80.64(6)
5 mg $133.30(9)
Zolmitriptan ZMT 5 mg $142.18(9)
Naratriptan (Amerge, GlaxoWellcome) 1, 2.5 mg $146.61(9)
Rizatriptan tablet (Canadian Maxalt, Merck) 5, 10 mg $91.46(6)
MLT 5, 10 mg $91.46(9)
Almotriptan (Axert, Pharmacia) 6.25, 12.5 mg $65.93(6)
Frovatriptan (Frova, Elan) 2.5 mg Not available

Almotriptan (Axert, Pharmacia), a second-generation triptan, received FDA approval in May of 2001. This new triptan was developed to improve potency and selectivity for the 5HT1B/1D receptor. Almotriptan also shows a high affinity for the 5-HT1F receptor located in the brain and periphery. This is a similarity among all of the 5-HT1 agonists. As previously mentioned, almotriptan works by stimulating the 5-HT1B receptors located on vascular smooth muscle, inducing vasoconstriction. Almotrip-tan also inhibits the release of inflammatory chemicals by stimulating the 5-HT1D receptor found on nerve fibers. Although structurally related to sumatriptan canadian, its vasoconstrictor properties in the meningeal arteries are 25 times more potent than suma-triptan. All the 5-HT1B/1D agonists are 3,5 substituted tryptamine derivatives, except for frovatriptan, which is a carbazole derivative.

Almotriptan is indicated for the acute treatment of migraine with or without aura. Almotriptan’s safety and efficacy in other types of headaches (i.e., cluster headache), as well as prophylactic therapy in migraine has not been established.

DOSAGES

Almotriptan is available as an oral formulation in doses of 6.25-mg and 12.5-mg tablets. The recommended dosage regimen of almotriptan is 6.25 mg or 12.5 mg at the onset of migraine, with a repeat dose in two hours if no relief is achieved (maximum daily dose is 25 mg/day). Expected decreases in the clearance of patients with hepatic and renal impairment warrant the dose to be started at 6.25 mg and not to exceed 12.5 mg/day in these patients. Approximately 45% of the drug is found unchanged in the urine and 13% is excreted via the fecal route.