Show simple item record Zádor Ferenc Balogh Mihály Váradi András Zádori Zoltán Sándor Király Kornél P Szűcs Edina Varga B Lázár Bernadette Hosztafi Sándor Riba Pál Benyhe Sándor Fürst Zsuzsanna Al-Khrasani Mahmoud 2018-02-21T16:07:04Z 2018-02-21T16:07:04Z 2017
dc.identifier.citation pagination=264-273;journalVolume=814;journalTitle=EUROPEAN JOURNAL OF PHARMACOLOGY; hu
dc.identifier.uri doi:10.1016/j.ejphar.2017.08.034
dc.description.abstract 14-O-methyl (14-O-Me) group in morphine-6-O-sulfate (M6SU) or oxymorphone has been reported to be essential for enhanced affinity, potency and antinociceptive effect of these opioids. Herein we report on the pharmacological properties (potency, affinity and efficacy) of the new compound, 14-O-methylmorphine (14-O-MeM) in in vitro. Additionally, we also investigated the antinociceptive effect of the novel compound, as well as its inhibitory action on gastrointestinal transit in in vivo. The potency and efficacy of test compound were measured by [35S]GTPgammaS binding, isolated mouse vas deferens (MVD) and rat vas deferens (RVD) assays. The affinity of 14-O-MeM for opioid receptors was assessed by radioligand binding and MVD assays. The antinociceptive and gastrointestinal effects of the novel compound were evaluated in the rat tail-flick test and charcoal meal test, respectively. Morphine, DAMGO, Ile5,6 deltorphin II, deltorphin II and U-69593 were used as reference compounds. 14-O-MeM showed higher efficacy (Emax) and potency (EC50) than morphine in MVD, RVD or [35S]GTPgammaS binding. In addition, 14-O-MeM compared to morphine showed higher affinity for mu-opioid receptor (MOR). In vivo, in rat tail-flick test 14-O-MeM proved to be stronger antinociceptive agent than morphine after peripheral or central administration. Additionally, both compounds inhibited the gastrointestinal peristalsis. However, when the antinociceptive and antitransit doses for each test compound are compared, 14-O-MeM proved to have slightly more favorable pharmacological profile. Our results affirm that 14-O-MeM, an opioid of high efficacy and affinity for MOR can be considered as a novel analgesic agent of potential clinical value.
dc.relation.ispartof urn:issn:0014-2999
dc.title 14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity. hu
dc.type Journal Article hu 2018-02-21T16:03:20Z
dc.language.rfc3066 en hu
dc.identifier.mtmt 3264775
dc.identifier.wos 000413779000031
dc.identifier.pubmed 28864212
dc.contributor.department SE/AOK/I/Farmakológiai és Farmakoterápiás Intézet
dc.contributor.department SE/GYTK/Gyógyszerészi Kémiai Intézet

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