Novel pyrrole based CB2 agonists: New insights on CB2 receptor role in regulating neurotransmitters' tone.
Eur J Med Chem
; 269: 116298, 2024 Apr 05.
Article
in En
| MEDLINE
| ID: mdl-38493727
ABSTRACT
The cannabinoid system is one of the most investigated neuromodulatory systems because of its involvement in multiple pathologies such as cancer, inflammation, and psychiatric diseases. Recently, the CB2 receptor has gained increased attention considering its crucial role in modulating neuroinflammation in several pathological conditions like neurodegenerative diseases. Here we describe the rational design of pyrrole-based analogues, which led to a potent and pharmacokinetically suitable CB2 full agonist particularly effective in improving cognitive functions in a scopolamine-induced amnesia murine model. Therefore, we extended our study by investigating the interconnection between CB2 activation and neurotransmission in this experimental paradigm. To this purpose, we performed a MALDI imaging analysis on mice brains, observing that the administration of our lead compound was able to revert the effect of scopolamine on different neurotransmitter tones, such as acetylcholine, serotonin, and GABA, shedding light on important networks not fully explored, so far.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cannabinoids
/
Receptor, Cannabinoid, CB2
Limits:
Animals
Language:
En
Journal:
Eur J Med Chem
Year:
2024
Document type:
Article
Affiliation country:
Publication country:
FR
/
FRANCE
/
FRANCIA
/
FRANÇA