PhD Scientific Days 2024

Poster Session B - Pharmaceutical Sciences and Health Technologies 1.

Inhibition of synaptic monoamine uptake by tolperisone

Előadó neve

Ms. Lóska, Dóra

Neptun code

ZAAQQ5

Előadó munkahelye

Department of Pharmacodynamics

Előadó telefonszáma

+36202957541

Előadó e-mail címe

loska.dorka@gmail.com

Az előadás címe

Inhibition of synaptic monoamine uptake by tolperisone

Szerző(k) neve és munkahelye

Dóra Lóska¹, Péter P. Lakatos¹, Márton Jakabos¹, Tamás Tábi¹

1: Department of Pharmacodynamics

Bemutatás módja

Poszter

Szekció

Poster Session B - Pharmaceutical Sciences and Health Technologies 1.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Tolperisone is a centrally acting muscle relaxant (CMR). Our research group previously reported it is capable of alleviating the symptoms of neuropathic pain in an animal model. Potent voltage-dependent sodium channel and weak calcium channel inhibition was demonstrated to play a role in its antinociceptive effect, while other, as yet unknown mechanisms may also contribute. Serotonin and noradrenaline reuptake inhibitors are first-line medications in the therapy of neuropathic pain that inhibit nociception by enhancing descending monoaminergic pathways.
Aims: Our aim was to develop a synaptosome model suitable for studying synaptic monoamine transport and to investigate the effect of tolperisone and other CMRs on synaptic monoamine uptake.
Method: The effect of tolperisone and known reuptake inhibitors on monoamine uptake was examined using rat brain synaptosomes. 4-(4-(Dimethylamino)styryl)-N-methylpyridinium (ASP+) a selective monoamine transporter substrate was used to assess monoamine transport by measuring its intracellular accumulation by fluorescence detection.
Results: Concentration-dependent and saturable ASP+ uptake into synaptosomes was detected. Ten µM ASP+ was chosen for further experiments as it was in the linear part of the curve. It was concentration-dependently inhibited by known monoamine-reuptake inhibitors according to their selectivity demonstrating the applicability of the model. Two hundred µM desipramine exerted 39% inhibition, while 66% and 14% inhibition were achieved by 200 µM duloxetine and citalopram, respectively. Tolperisone also inhibited ASP+ uptake in a concentration-dependent manner (15% inhibition at 800 µM), which may contribute to its antinociceptive effect. ASP+ uptake was not reduced by sodium or calcium channel blockers indicating that tolperisone directly inhibits monoamine transporters. Monoamine uptake was not affected by other CMRs, such as tizanidine and baclofen, while clonidine significantly reduced synaptic ASP+ uptake (19% inhibition at 800 µM).
Conclusion: A fast and high throughput method for studying synaptic monoamine transport was optimized. Inhibitory effect of tolperisone on monoamine uptake was identified, which, along with its inhibition of ion channels likely contributes to its analgesic effect reported in neuropathic pain.
Funding: The work was supported by ÚNKP-23-2-I-SE-46 grant.

University

Semmelweis University

Other university, not listed above

-

Supervisor

Tamás Tábi

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8244

Start

15:45

End

15:48