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dc.creatorPecikoza, Uroš
dc.creatorMicov, Ana
dc.creatorTomić, Maja
dc.creatorStepanović-Petrović, Radica
dc.date.accessioned2019-09-02T12:03:46Z
dc.date.available2019-09-02T12:03:46Z
dc.date.issued2018
dc.identifier.issn0024-3205
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3061
dc.description.abstractAims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, propranolol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors.en
dc.publisherPergamon-Elsevier Science Ltd, Oxford
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS//
dc.rightsrestrictedAccess
dc.sourceLife Sciences
dc.subjectEslicarbazepine acetateen
dc.subjectTrigeminal painen
dc.subjectOrofacial formalin testen
dc.subjectAdrenergic receptorsen
dc.subjectCholinergic receptorsen
dc.subjectOpioid receptorsen
dc.titleEslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptorsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПецикоза, Урош; Степановић-Петровић, Радица; Мицов, Aна; Томић, Маја;
dc.citation.volume214
dc.citation.spage167
dc.citation.epage175
dc.citation.other214: 167-175
dc.citation.rankM21
dc.identifier.wos000450360000019
dc.identifier.doi10.1016/j.lfs.2018.10.059
dc.identifier.pmid30393024
dc.identifier.scopus2-s2.0-85055971551
dc.identifier.rcubconv_4260
dc.type.versionpublishedVersion


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