PhD Scientific Days 2017

Oral Presentations: Pharmaceutical

Novel opioid produces measurable peripheral antinociception after local or systemic administration

Előadó neve

Balogh, Mihály

Előadó munkahelye

Semmelweis University Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36703993069

Előadó e-mail címe

balogh.mihaly@med.semmelweis-univ.hu

Az előadás címe

Novel opioid produces measurable peripheral antinociception after local or systemic administration

Szerző(k) neve és munkahelye

Mihály Balogh(1), Kornél Király (1), Bence Varga(1), Richard Ármós(1), Pál Riba(1), Ferenc Zádor(2), Zoltán Zádori(1), Sándor Hosztafi(3), András Váradi(3), Zsuzsanna Fürst(1), Mahmoud Al-Khrasani(1),
(1) Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest
(2) Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged
(3) Department of Pharmaceutical Chemistry, Semmelweis University, Budapest

Szekció

Oral Presentations: Pharmaceutical

Data of the presenter

Doctoral School: Pharmaceutical Sciences
Program: Experimental and Clinical Pharmacology
Supervisor: Mahmoud Al-Khrasani
E-mail address: balogh.mihaly@med.semmelweis-univ.hu

Text of the abstract

Growing evidences support the contribution of peripheral opioid receptors to the total antinociception produced by systemic opioids. Peripheral antinociception has been reported to be pain model and drug physicochemical property dependent.
The present study was aimed to assess the antinociceptive effect of 14-O-methylmorphine-6-O-sulfate (14-O-MeM6SU), opioid agonist with high efficacy compared to morphine in the rat formalin test after systemic or local administration.
Method: briefly, drugs were injected subcutaneously (s.c.) or intraplantarly (i.pl.), 15 or 5 min prior to i.pl. injections of formalin, respectively. The pain events were counted for 60 min, which was further subdivided into 5 min time periods. To assess the action of the test compounds two phases were constructed, phase I (0-10min) and phase II (11-60min) as described previously (Abbott et al., 1995). In addition, “Righting reflex” method was used to determine the impact of test compounds on sleeping time induced by inhaled isoflurane. Vehicle injections were used as control. The results were considered to be statistically significant when p < 0.05.
Results: S.c. injections of 14-O-MeM6SU or morphine inhibited the pain events evoked by i.pl. formalin in both phases (I and II). Coadministered naloxone methiodide, a peripherally acting opioid antagonist inhibited the antinociceptive effect of certain s.c. 14-O-MeM6SU doses but not morphine. Ipsilateral or contralateral injections of morphine decreased the pain events in both phases. Interestingly, 14-O-MeM6SU in certain doses produced antinociception after ipsilateral but not contralateral administrations. To assess the CNS penetration of test compounds, indirect method, the prolongation of the sleeping time of isoflurane by opioids was applied. Morphine in s.c. antinociceptive doses but not 14-O-MeM6SU significantly prolonged the sleeping time.
These results indicate that MOR agonists with high efficacy and limited access to CNS may have peripheral antinociception that is of potential clinical value.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1027

Authors (legacy)

Mihály Balogh(1), Kornél Király (1), Bence Varga(1), Richard Ármós(1), Pál Riba(1), Ferenc Zádor(2), Zoltán Zádori(1), Sándor Hosztafi(3), András Váradi(3), Zsuzsanna Fürst(1), Mahmoud Al-Khrasani(1),
(1) Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest
(2) Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged
(3) Department of Pharmaceutical Chemistry, Semmelweis University, Budapest