Novel pyrrole based CB2 agonists: New insights on CB2 receptor role in regulating neurotransmitters' tone

• DOI: 10.1016/j.ejmech.2024.116298
• Publication Date: 2024-03-11T16:24:13Z
• Authors: Simone Di Micco; Tania Ciaglia; Emanuela Salviati; Perrone Michela; Magdalena Kostrzewa; Simona Musella; Aniello Schiano M...; Veronica Di Sarno; Gerardina Smaldone; Francesca Di Matteo; Ilaria Capolupo; Rosmara Infantino; Giuseppe Bifulco; Giacomo Pepe; Eduardo M. Sommella; Poulami Kumar; Manuela Giovanna ...; Marco Allarà; Nuria Sánchez-Fer...; Ester Aso; Isabel M. Gomez-M...; Pietro Campiglia; Carmine Ostacolo; Sabatino Maione; Alessia Ligresti; Alessia Bertamino
• Keywords: Cannabinoid 2 receptor agonists; In silico design; In vitro analysis; In vivo characterization; Maldi-imaging assays; Cannabinoid 2 receptor agonists; In silico design; In vitro analysis; In vivo characterization; Maldi-imaging assays.; In silico design, Cannabinoid 2 receptor agonists, In vitro analysis, In vivo characterization, Maldi-imaging assays

The cannabinoid system is one of the most investigated neuromodulatory systems because its involvement in multiple pathologies such as cancer, inflammation, and psychiatric diseases. Recently, CB2 receptor has gained increased attention considering crucial role modulating neuroinflammation several pathological conditions like neurodegenerative Here we describe rational design pyrrole-based analogues, which led to a potent pharmacokinetically suitable full agonist particularly effective improving cognitive functions scopolamine-induced amnesia murine model. Therefore, extended our study by investigating interconnection between activation neurotransmission this experimental paradigm. To purpose, performed MALDI imaging analysis on mice brains, observing that administration lead compound was able revert effect scopolamine different neurotransmitter tones, acetylcholine, serotonin, GABA, shedding light important networks not fully explored, so far.