Indications
Zolmitriptan is prescribed for the acute management of migraine episodes, with or without aura, in adult patients aged 18 years and older.
Pharmacodynamics
Zolmitriptan functions as a selective agonist of the serotonin (5-hydroxytryptamine; 5-HT) receptors, with particular specificity for the 5-HT1B and 5-HT1D receptor subtypes. By activating·hese receptors, zolmitriptan is believed to alleviate migraine symptoms. It also acts as a vasoconstrictor, which can potentially cause cardiovascular side effects such as myocardial ischemia or infarction, arrhythmias, strokes, and other vascular issues. Additionally, patients may experience symptoms like pain and pressure in the chest, throat, neck, or jaw, as well as the risk of medication overuse headaches and serotonin syndrome. Patients with phenylketonuria should be informed that ZOMIG-ZMT contains phenylalanine.
Absorption
Zolmitriptan tablets have a mean oral bioavailability of approximately 40%, unaffected by food intake. Its pharmacokinetics remains linear within a dosage rang·h 75% of the maximum concentration (Cmax) reached within one hour post-dosing·he median time to achieve maximum plasma concentration (Tmax) is 1.5 hours for the tablet and 3 hours for the orally disintegrating·he area under the curve (AUC) rang·h, while Cmax is between 16 and 25.2 ng·hen administered as a nasal spray, zolmitriptan is detected in the plasma within 2-5 minutes, compared to 10-15 minutes for the oral tablet. This faster absorption is attributed to its uptake through the nasal mucosa, with a bioavailability of 102% relative to the tablet. Plasma concentrations are maintained for approximately 4-6 hours following·he active N-desmethyl metabolite of zolmitriptan achieves about two-thirds the plasma concentration of zolmitriptan, irrespective of the administration route.
Metabolism
Zolmitriptan undergoes hepatic metabolism, predominantly via the cytochrome P450 enzyme CYP1A2 and monoamine oxidase (MAO). Its metabolism results in three main metabolites: an active N-desmethyl metabolite (183C91), and two inactive metabolites, N-oxide (1652W92) and indole acetic acid (2161W92). Studies using·hrome P450 inhibitors, such as cimetidine, support the involvement of these metabolic pathways.
Mechanism of Action
Zolmitriptan functions primarily by modulating nociceptive nerve signaling within the central nervous system, specifically targeting the 5-HT1B/1D receptors located throughout the trigeminocervical complex and related brain regions. This modulation is pivotal in managing migraines, which are multifaceted events characterized by unilateral throbbing headaches, sensitivity to light, and other sensory aversions. Migraines typically progress through several phases: the premonitory phase, marked by irritability and fatigue; the headache phase, lasting anywhere from four to 72 hours; and the postdrome phase, which can linger for up to a day with symptoms akin to those seen earlier. Additionally, some individuals may experience neurological deficits known as migraine aura, often preceding the headache phase. The pathophysiology underpinning migraines is complex, involving both neurological and vascular elements. It is thought that migraine-related head pain results from the activation of nociceptive nerves within the trigeminocervical complex. These nerves release vasoactive peptides, like calcitonin gene-related peptide (CGRP), causing cranial vasodilation. Zolmitriptan further enhances vasoconstriction through direct 5-HT1B-mediated action on cranial blood vessels and 5-HT1D-mediated inhibition of CGRP release. Although traditionally characterized by their effects on 5-HT1B/1D receptors, triptans like zolmitriptan also act as 5-HT1F agonists. The 5-HT1F subtype is prevalent in the trigeminocervical complex but not significantly present within cerebral vasculature, and the implications of 5-HT1F activation are not yet fully understood. Cortical spreading depression, which can originate in the ipsilateral parietal region, may also engage 5-HT1B/1D receptor pathways, indicating that triptans might address symptoms associated with this phenomenon as well.
