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dc.contributor.author Balogh, Mihály
dc.contributor.author Zádor, Ferenc
dc.contributor.author Zádori, S. Zoltán
dc.contributor.author Shaqura, Mohammed
dc.contributor.author Király, Kornél P.
dc.contributor.author Mohammadzadeh, Amir
dc.contributor.author Varga, K. Bence
dc.contributor.author Lázár, Bernadette
dc.contributor.author Mousa, A. Shaaban
dc.contributor.author Hosztafi, Sándor
dc.contributor.author Riba, Pál
dc.contributor.author Benyhe, Sándor
dc.contributor.author Gyires, Klára
dc.contributor.author Schäfer, Michael
dc.contributor.author Fürst, Susanna
dc.contributor.author Al-Khrasani, Mahmoud
dc.date.accessioned 2020-01-27T10:35:35Z
dc.date.available 2020-01-27T10:35:35Z
dc.date.issued 2019
dc.identifier 85068475051
dc.identifier.citation journalVolume=10;pagination=347,pages:16;journalTitle=FRONTIERS IN PHARMACOLOGY;journalAbbreviatedTitle=FRONT PHARMAC;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/7972
dc.identifier.uri doi:10.3389/fphar.2019.00347
dc.description.abstract Reduction of the opioid analgesia in diabetic neuropathic pain (DNP) results from mu-opioid receptor (MOR) reserve reduction. Herein, we examined the antinociceptive and antiallodynic actions of a novel opioid agonist 14-O-methymorphine-6-O-sulfate (14-O-MeM6SU), fentanyl and morphine in rats with streptozocin-evoked DNP of 9-12 weeks following their systemic administration. The antinociceptive dose-response curve of morphine but not of 14-O-MeM6SU or fentanyl showed a significant right-shift in diabetic compared to non-diabetic rats. Only 14-O-MeM6SU produced antiallodynic effects in doses matching antinociceptive doses obtained in non-diabetic rats. Co-administered naloxone methiodide (NAL-M), a peripherally acting opioid receptor antagonist failed to alter the antiallodynic effect of test compounds, indicating the contribution of central opioid receptors. Reduction in spinal MOR binding sites and loss in MOR immunoreactivity of nerve terminals in the spinal cord and dorsal root ganglia in diabetic rats were observed. G-protein coupling assay revealed low efficacy character for morphine and high efficacy character for 14-O-MeM6SU or fentanyl at spinal or supraspinal levels (E-max values). Furthermore, at the spinal level only 14-O-MeM6SU showed equal efficacy in G-protein activation in tissues of diabetic- and non-diabetic animals. Altogether, the reduction of spinal opioid receptors concomitant with reduced analgesic effect of morphine may be circumvented by using high efficacy opioids, which provide superior analgesia over morphine. In conclusion, the reduction in the analgesic action of opioids in DNP might be a consequence of MOR reduction, particularly in the spinal cord. Therefore, developing opioids of high efficacy might provide analgesia exceeding that of currently available opioids.
dc.title Efficacy-based perspective to overcome reduced opioid analgesia of advanced painful diabetic neuropathy in rats
dc.type Journal Article
dc.date.updated 2019-11-20T14:17:08Z
dc.language.rfc3066 en
dc.rights.holder NULL
dc.identifier.mtmt 30626189
dc.identifier.wos 000463932900004
dc.identifier.pubmed 31024314
dc.contributor.department SE/AOK/I/Farmakológiai és Farmakoterápiás Intézet
dc.contributor.department SE/GYTK/Gyógyszerészi Kémiai Intézet
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote Funding Agency and Grant Number: Ministry of Human Capacities, Hungary (New National Excellence Program) [UNKP-17-4, UNKP-18-3-III]; National Research Development and Innovation Office (NKFIH, Hungary) [OTKA 108518, FK 124878] Funding text: This work was supported by the Ministry of Human Capacities, Hungary (New National Excellence Program: UNKP-17-4 awarded to ZZ and UNKP-18-3-III awarded to MB), and the National Research Development and Innovation Office (NKFIH, Hungary, Grant Nos. OTKA 108518 and FK 124878). Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Berlin, Germany Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary Cited By :1 Export Date: 17 August 2019 Correspondence Address: Al-Khrasani, M.; Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis UniversityHungary; email: al-khrasani.mahmoud@med.semmelweis-univ.hu Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary Department of Anaesthesiology and Intensive Care Medicine, Charité University Berlin, Berlin, Germany Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary Cited By :1 Export Date: 13 September 2019 Correspondence Address: Al-Khrasani, M.; Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis UniversityHungary; email: al-khrasani.mahmoud@med.semmelweis-univ.hu


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