PhD Scientific Days 2026

Poster Session 3.N - Neurosciences

IPAP vs. β-PEA Activity at TAAR1

Előadó neve

Dr. Chalabiani, Yashar

Neptune code

BX7TGL

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

0036702389961

Előadó e-mail címe

chalabiani.yashar@semmelweis.hu

Az előadás címe

IPAP vs. β-PEA Activity at TAAR1

Szerző(k) neve és munkahelye

Yashar Chalabiani¹, Brachyahu Meir Kestecher², Sayam Ghosal², Aliz Judit Ernyey¹, László Gábor Hársing Jr¹, Xabier Osteikoetxea², Ildikó Miklya¹

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2: Institute of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session 3.N - Neurosciences

Language of the presentation

English

Preferred session

Neurosciences

Összefoglaló szövege

Introduction
Trace amine–associated receptor 1 (TAAR1) is an intracellular, pleiotropic G protein–coupled receptor (GPCR) activated by endogenous trace amines such as β phenethylamine (β-PEA) and tryptamine (TRP), and it is also engaged by monoamine-releasing agents (MRAs) including amphetamine and methamphetamine. At low concentrations, β-PEA and TRP can act as monoaminergic activity enhancers (MAEs), preferentially facilitating vesicular neurotransmitter release, whereas MRAs trigger both vesicular release and non-vesicular, transporter-mediated monoamine efflux.  

Aims
We aimed to investigate the MOA of the synthetic MAE compound (−)-IPAP at TAAR1 by measuring receptor-mediated cAMP accumulation in rat-TAAR1-expressing Expi293F suspension cells.

Methods
Dose–response curves (10⁻¹⁰–10⁻⁴ M) were generated for β-phenethylamine (β-PEA; Sigma-Aldrich) and 1-(indol-3-yl)-2-propylaminopentane ((−)-IPAP; Fujimoto Pharmaceutical Corp) using seven-point serial dilutions prepared in assay buffer and applied to rTAAR1-expressing Expi293F cells to quantify TAAR1-mediated cAMP accumulation.
rTAAR1 cDNA (rTAAR1; GeneWiz) was cloned into the pcDNA3 mammalian expression vector with a CMV promoter. The plasmid was transformed into DH5α and grown using ampicillin selection. Plasmids were isolated and purified using a plasmid preparation kit, and sequenced prior to use. Expi293F suspension cells were transiently transfected using polyethyleneimine. After 48–72 h, receptor expression was confirmed by PCR, and cells were harvested immediately before the assay. cAMP accumulation was measured using the Revvity cAMP-Gs Dynamic homogeneous time-resolved fluorescence (HTRF) assay, a competitive immunoassay based on HTRF. Fluorescence ratios (665 nm/620 nm) were plotted against a compound concentration, signals were inversely proportional to intracellular cAMP levels. EC₅₀ values were determined using 4-parameter logistic (4PL) non-linear regression.

Result
In rTAAR1-expressing Expi293F cells, cAMP responses were normalised to the maximal response evoked by β-PEA; 100%. (−)-IPAP produced a robust, concentration-dependent increase in cAMP with slightly reduced maximal efficacy, reaching ~90% of the β-PEA Emax.

Conclusion
This profile supports (−)-IPAP as a TAAR1 agonist consistent with an MAE-like pharmacological signature rather than an MRA-like pattern.

Funding
SE250+

University

Semmelweis University

Supervisor

Ildikó Miklya

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

9225

Start

13:42

End

13:45