PhD Scientific Days 2020

Pharmaceutical Sciences I. Lectures

Pharmacological Characterization of Somatostatin 4 Receptor Agonists, as Novel Analgesic Candidates

Előadó neve

Dr. Kántás, Boglárka

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs & Szentágothai Research Centre and Centre for Neuroscience, University of Pécs

Előadó telefonszáma

72/536-217/31915

Előadó e-mail címe

kantas.boglarka@gmail.com

Az előadás címe

Pharmacological Characterization of Somatostatin 4 Receptor Agonists, as Novel Analgesic Candidates

Szerző(k) neve és munkahelye

Boglárka Kántás 1, Éva Szőke 1,5, Ádám Horváth 1, Péter Bánhegyi 3, Rita Börzsei 2, Ágnes Hunyady 1, Éva Borbély 1, Csaba Hetényi 2, Erika Pintér 1,4,5, Zsuzsanna Helyes 1,4,5
1 Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs & Szentágothai Research Centre and Centre for Neuroscience, University of Pécs
2 Department of Pharmacology, Faculty of Pharmacy, University of Pécs
3 Avicor Ltd., Budapest, Hungary
4 PharmInVivo Ltd., Pécs, Hungary
5 Algonist GmbH, Wien, Austria

Szekció

Pharmaceutical Sciences I. Lectures

Language of the presentation

English

Section, first choice

Pharmaceutical Sciences

Section, second choice

Neurosciences

Összefoglaló szövege

Introduction: Our group has previously provided several lines of evidence that somatostatin released from the capsaicin-sensitive peptidergic nociceptors mediates analgesic and anti-inflammatory effects via its sst4 receptor without influencing endocrine functions. Therefore, sst4 is suggested to be a novel target for drug development, especially in chronic neuropathic pain, which is a huge unmet medical need.
Aims: We investigated the binding, receptor activation abilities, and the effects of our four novel small molecule sst4 receptor agonists in mouse models of chronic neuropathic pain and acute neurogenic inflammatory hyperalgesia.
Methods: We examined the in silico binding and sst4-linked G protein activation of our novel small molecule pyrrolo-pyrimidine compounds on stable sst4 expressing CHO cells (1 nM-10 μM). The effects of the two most potent ligands were tested on thermal and mechanical hyperalgesia in the resiniferatoxin-induced acute neurogenic inflammation (500 µg/kg p.o.) and mechanical hyperalgesia in the partial sciatic nerve ligation-induced traumatic mononeuropathy (20, 100, 500, 1000, 2000 µg/kg p.o.) models in mice.
Results: All our four tested compounds bind to the same high affinity binding site of sst4 as the reference compound J-2156 and are able to activate the sst4-linked G protein. The 500 µg/kg dose of one compound significantly reduces neurogenic inflammatory thermal and mechanical hyperalgesia, and two of them exert significant, 60-70% maximal anti-hyperalgesic effects in the neuropathy model after a single administration on the 7th postoperative day.
Conclusion: Our novel, orally active small molecule sst4 agonists can open promising analgesic drug developmental perspectives for inflammatory and neuropathic pain.
Support: National Brain Research Program 20017-1.2.1-NKP-2017-00002, GINOP-2.3.2-15-2016-00050, GINOP-2.3.2-15-2016-00048 and EFOP-3.6.2-16-2017-00008, Gedeon Richter's Talentum Foundation, János Bolyai fellowship, ÚNKP-19-3 New National Excellence Program of the Ministry for Innovation and Technology.

Additional Information

Supervisors:
Zsuzsanna Helyes, zsuzsanna.helyes@aok.pte.hu
Éva Borbély, eva.borbely@aok.pte.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4649

Start

10:10

End

10:25

Authors (legacy)

Boglárka Kántás 1, Éva Szőke 1,5, Ádám Horváth 1, Péter Bánhegyi 3, Rita Börzsei 2, Ágnes Hunyady 1, Éva Borbély 1, Csaba Hetényi 2, Erika Pintér 1,4,5, Zsuzsanna Helyes 1,4,5
1 Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs & Szentágothai Research Centre and Centre for Neuroscience, University of Pécs
2 Department of Pharmacology, Faculty of Pharmacy, University of Pécs
3 Avicor Ltd., Budapest, Hungary
4 PharmInVivo Ltd., Pécs, Hungary
5 Algonist GmbH, Wien, Austria