PhD & Postdoc

Emilia Wiśniewska

Neuropharmacology · Jagiellonian University

Emilia Wiśniewska characterises the pharmacological properties of a novel series of metabotropic glutamate receptor 5 negative allosteric modulators at the Jagiellonian University's Department of Neurobiology, working under Prof. Andrzej Pilc, whose group originally pioneered mGluR-targeted antidepressant research in Poland. Unlike standard antidepressants that target monoamine systems, mGluR5 NAMs act within minutes in acute rodent models and maintain efficacy in learned helplessness paradigms resistant to SSRIs — making them attractive for treatment-resistant depression. Emilia has conducted systematic structure–activity studies across 18 analogues, correlating radioligand binding kinetics (measured by KinIQ methodology) with in vivo pharmacokinetics and CNS penetration assessed by LC-MS/MS in rat brain microdialysate. Her lead compound achieves K_off = 0.0017 min⁻¹ — a slow-off kinetic profile associated with prolonged receptor engagement — and brain-to-plasma ratio of 4.2, combining two properties rarely achieved simultaneously in this chemotype. An industry collaboration with Celon Pharma funds analogue synthesis and GLP toxicology, and a PCT patent application covers the optimal compound series. Emilia's imminent ECNP conference presentation will establish her profile in European CNS drug discovery circles.

Thesis Topic

mGluR5 Negative Allosteric Modulators as Novel Antidepressants: Binding Kinetics, CNS Penetration, and Chronic Rodent Efficacy

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