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The Effects of Levetiracetam, Sumatriptan, and Caffeine in a Rat Model of Trigeminal Pain: Interactions in 2-Component Combinations
dc.creator | Tomić, Maja | |
dc.creator | Pecikoza, Uroš | |
dc.creator | Micov, Ana | |
dc.creator | Popović, Božidar V. | |
dc.creator | Stepanović-Petrović, Radica | |
dc.date.accessioned | 2019-09-02T11:46:35Z | |
dc.date.available | 2019-09-02T11:46:35Z | |
dc.date.issued | 2015 | |
dc.identifier.issn | 0003-2999 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/2385 | |
dc.description.abstract | BACKGROUND: Levetiracetam is an antiepileptic drug with analgesic efficacy shown in pain models and small clinical trials. Sumatriptan is used in acute migraine treatment. Caffeine is widely consumed in some beverages/foods and is also an adjuvant in analgesic formulations. We examined the effects of systemic levetiracetam, sumatriptan, and caffeine and their interactions in 2-component combinations in the rat orofacial formalin test, a model of trigeminal pain. METHODS: Rats received a subcutaneous injection of formalin solution into the perinasal area, and the total time spent in nociceptive behavior (face rubbing) was quantified. The antinociceptive effect of drugs/drug combinations was assessed 1 hour after per os administration. The type of interaction between levetiracetam/sumatriptan and caffeine was examined by comparing the effects of a fixed, effective dose of levetiracetam/sumatriptan alone with the effects of the same dose applied with increasing, subeffective doses of caffeine. The type of interaction between levetiracetam and sumatriptan was determined by isobolographic analysis. RESULTS: Levetiracetam (1-50 mg/kg) and sumatriptan (0.5-5 mg/kg) produced significant and dose-dependent antinociceptive effects in both phases of the orofacial formalin test (P = 0.001). Caffeine (7.5-100 mg/kg) produced significant antinociception in the second phase of the test (P = 0.04). Caffeine (1-7.5 mg/kg) significantly reduced the antinociceptive effects of levetiracetam (25 mg/kg) (first phase P = 0.002, second phase P lt 0.001) and sumatriptan (2.5 mg/kg) (first phase P = 0.014, second phase P = 0.027); dose-dependent inhibition was observed in the second phase. Levetiracetam and sumatriptan exerted an additive interaction in the second phase of the orofacial formalin test. CONCLUSIONS: Results indicate that levetiracetam may be useful for treatment of pain in the trigeminal region. Dietary caffeine might decrease the effects of levetiracetam and sumatriptan; this needs to be considered in clinical settings. A levetiracetam-sumatriptan combination could also be useful in trigeminal pain treatment. Its efficacy and adverse effects should be examined clinically. | en |
dc.publisher | Lippincott Williams & Wilkins, Philadelphia | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS// | |
dc.rights | restrictedAccess | |
dc.source | Anesthesia and Analgesia | |
dc.title | The Effects of Levetiracetam, Sumatriptan, and Caffeine in a Rat Model of Trigeminal Pain: Interactions in 2-Component Combinations | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Степановић-Петровић, Радица; Томић, Маја; Мицов, Aна; Поповић, Божидар В.; Пецикоза, Урош; | |
dc.citation.volume | 120 | |
dc.citation.issue | 6 | |
dc.citation.spage | 1385 | |
dc.citation.epage | 1393 | |
dc.citation.other | 120(6): 1385-1393 | |
dc.citation.rank | aM21 | |
dc.identifier.wos | 000354864100030 | |
dc.identifier.doi | 10.1213/ANE.0000000000000640 | |
dc.identifier.pmid | 25710675 | |
dc.identifier.scopus | 2-s2.0-84937920174 | |
dc.type.version | publishedVersion |