14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity (NDA@SZTAKI, Nemzeti Digitális Adattár, National Digital Data Archive)

14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity

Metaadatok

Tartalom:	http://real.mtak.hu/64816/
Archívum:	MTA Könyvtár
Gyûjtemény:	Status = Published Type = Article
Cím:	14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity
Létrehozó:	ZÃ¡dor, Ferenc Balogh, Mihaly VÃ¡radi, AndrÃ¡s ZÃ¡dori, ZoltÃ¡n S. KirÃ¡ly, KornÃ©l SzÅ±cs, Edina Varga, Bence LÃ¡zÃ¡r, Bernadette Hosztafi, SÃ¡ndor Riba, PÃ¡l Benyhe, SÃ¡ndor FÃ¼rst, Zsuzsanna Al-Khrasani, Mahmoud
Kiadó:	Elsevier
Dátum:	2017-08-30
Téma:	R850-854 Experimental medicine / kisÃ©rleti orvostudomÃ¡ny
Tartalmi leírás:	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]GTPÎ³S 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]GTPÎ³S binding. In addition, 14-O-MeM compared to morphine showed higher affinity for Î¼-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.
Nyelv:	magyar magyar
Típus:	Article PeerReviewed info:eu-repo/semantics/article
Formátum:	text text
Azonosító:	http://real.mtak.hu/64816/1/14-O-Metilmorfin_EJP2017.pdf http://real.mtak.hu/64816/7/ZadorEurJPharm2.pdf ZÃ¡dor, Ferenc and Balogh, Mihaly and VÃ¡radi, AndrÃ¡s and ZÃ¡dori, ZoltÃ¡n S. and KirÃ¡ly, KornÃ©l and SzÅ±cs, Edina and Varga, Bence and LÃ¡zÃ¡r, Bernadette and Hosztafi, SÃ¡ndor and Riba, PÃ¡l and Benyhe, SÃ¡ndor and FÃ¼rst, Zsuzsanna and Al-Khrasani, Mahmoud (2017) 14-O-Methylmorphine: A Novel Selective Mu-Opioid Receptor Agonist with High Efficacy and Affinity. EUROPEAN JOURNAL OF PHARMACOLOGY. ISSN 0014-2999
Kapcsolat:	http://real.mtak.hu/64816/ https://doi.org/10.1016/j.ejphar.2017.08.034 DOI:10.1016/j.ejphar.2017.08.034