Beyond its anti‐migraine properties, sumatriptan is an anti‐inflammatory agent: A systematic review

Abstract

Sumatriptan is the first available medication from triptans family that was approved by the U.S. Food and Drug Administration for migraine attacks and cluster headaches in 1991. Most of its action is mediated by selective 5‐HT1B/1D receptor agonism. Recent investigations raised the possibility of repositioning of this drug to other indications beyond migraine, as increasing evidence suggests for an anti‐inflammatory property of sumatriptan. We performed a literature search using PubMed, Web of Science, Scopus, and Google Scholar using “inflammation AND sumatriptan” or “inflammation AND 5HT1B/D” as the keywords. Then, articles were screened for their relevance and those directly discussing the correlation between inflammation and sumatriptan or 5HT1B/D were included. Total references reviewed or inclusion/exclusion were 340 retrieved full‐text articles (n = 340), then based on critical assessment 66 of them were included in this systematic review. Our literature review indicates that at low doses, sumatriptan can reduce inflammatory markers (e.g., interleukin‐1β, tumor necrosis factor‐α, and nuclear factor‐κB), affects caspases and changes cells lifespan. Additionally, nitric oxide synthase and nitric oxide signaling seem to be regulated by this drug. It also inhibits the release of calcitonin gene‐related peptide. Sumatriptan protects against many inflammatory conditions including cardiac and mesenteric ischemia/reperfusion, skin flap, pruritus, peripheral, and central nervous system injuries such as spinal cord injury, testicular torsion‐detorsion, oral mucositis, and other experimental models. Considering the safety and potency of low dose sumatriptan compared to corticosteroids and other immunosuppressive medications, it is worth to take advantage of sumatriptan in inflammatory conditions.

Bergapten Attenuates Nitroglycerin-Induced Migraine Headaches through Inhibition of Oxidative Stress and Inflammatory Mediators

“…It is considered a successful migraine therapy with well-established scientific rationale especially in reversing thermal and mechanical allodynia . The therapeutic potential of sumatriptan reported in previous literature is not only limited to neurogenic inflammation but also has an effect on myocardial ischemia, skin flap necrosis, testicular torsion, visceral pain, spinal cord injury, neuropathy, seizures, opioid addiction, rhinitis, radiotherapy-induced oral mucositis, and cisplatin-induced renal injury . The current study aimed to investigate the headache-relieving potential of bergapten, employing behavioral, antioxidant, and molecular investigations.…”

Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia

“…In a study of healthy females receiving sumatriptan, it has been shown that sumatriptan caused a significant decrease in reaction time for recognition of words compared to placebo, suggesting CNS effects of sumatriptan [77]. In addition to its antimigraine properties via activation of serotonin 5HT 1B/D autoreceptors, sumatriptan has been recognized as an anti-inflammatory agent [78]. Current evidence from preclinical studies suggests that low doses of sumatriptan are useful in many inflammatory conditions, which has to be further investigated in clinical studies [78].…”

“…In addition to its antimigraine properties via activation of serotonin 5HT 1B/D autoreceptors, sumatriptan has been recognized as an anti-inflammatory agent [78]. Current evidence from preclinical studies suggests that low doses of sumatriptan are useful in many inflammatory conditions, which has to be further investigated in clinical studies [78].…”

Gepants for Acute and Preventive Migraine Treatment: A Narrative Review

“…The development of this drug was a benchmark for the acute therapy and pathophysiology of migraine. It was first assumed that triptans possibly relieved pain by direct vasoconstriction and regulation of trigeminal inflammatory transmitter release [ 11 ]. Over the last decades, preventive migraine therapy relied on medications not specifically developed for migraine management.…”