PhD Scientific Days 2025

Poster Session II. - G: Pharmaceutical Sciences and Health Technologies

Investigation of the Mechanism of Action of Enhancer Substance via TAAR1

Name of the presenter

Chalabiani Yashar

Institute/workplace of the presenter

Department of Pharmacology and Pharmacotherapy

Authors

Yashar Chalabiani¹, Ildiko Miklya¹, Hársing László Gábor Jr¹, Aliz Judit Ernyey¹

1: Department of Pharmacology and Pharmacotherapy

Text of the abstract

Investigation of Mechanism of Action of Enhancer Substances via TAAR1
Yashar Chalabiani, Aliz Judit Ernyey, Hársing László Gábor Jr, Ildiko Miklya
Semmelweis University, Department of Pharmacology and Pharmacotherapy
Introduction:
Monoaminergic activity enhancers (MAEs) are a novel class of compounds that selectively enhance action potential-evoked monoamine release, distinct from classical monoamine releasing agents (MRAs). MAEs exert their effects through activation of trace amine-associated receptor 1 (TAAR1), which modulates dopaminergic and GABAergic neurotransmission.
Aims:
To elucidate the mechanism by which the enhancer compound (-)BPAP modulates neurotransmitter release via TAAR1 signaling.
Methods:
Two sets of experiments were performed.
1. cAMP Measurement: Ventral tegmental area (VTA) slices from female Long-Evans rats were incubated with BPAP (10⁻¹¹ M), BPAP plus the TAAR1 antagonist EPPTB (10⁻⁶ M), or saline (control) for 30 minutes. cAMP levels were quantified using a Mouse/Rat cAMP Immunoassay.
2. Dopamine Release: Striatal slices from adult male Wistar rats were incubated with (−)BPAP (10⁻¹² or 10⁻¹¹ M) or selegiline (10⁻⁹ M), with or without EPPTB (0.01–0.1 μM), in oxygenated Krebs-bicarbonate buffer. [³H]dopamine release was evoked by electrical stimulation and measured by liquid scintillation spectrometry.
Results:
BPAP significantly increased cAMP levels in VTA slices, an effect abolished by TAAR1 antagonism. In striatal slices, BPAP and selegiline selectively enhanced electrically evoked vesicular dopamine release in a Ca²⁺- and cAMP-dependent manner, without inducing reverse transport via DAT. EPPTB blocked these effects, confirming TAAR1 mediation.
Conclusion:
TAAR1-mediated enhancers like BPAP modulate neurotransmitter release via a mechanism distinct from MRAs, enhancing vesicular dopamine and GABA output through a cAMP-dependent pathway. These findings suggest TAAR1-targeting compounds have therapeutic potential in neuropsychiatric and neurodegenerative disorders.
Funding:
Supported by Semmelweis University, E250+ and Semmelweis University, Department of Pharmacology and Pharmacotherapy.
E-mail: yashar.chalabiani@gmail.com
University: Semmelweis University
Supervisor: Dr. Ildiko Miklya
Preferred presentation type: Poster