Mechanism of action: Purinergic receptor 2X, ligand-gated ion channel 7 (P2X7) antagonist

Preclinical pharmacology

AZ11657312 is a potent antagonist of the rat P2X7 receptor with a pA2 for inhibition of agonist-stimulated ethidium bromide release of 7.8 (15nM) in HEK cells expressing the recombinant rat P2X7 receptor. Treatment of rats with AZ11657312 (30-60mg/kg BID orally (plasma compound levels of at least 3 x pA2) resulted in a significant reduction in mechanical hyperalgesia and disease severity in the streptococcal cell wall model of arthritis, and a delay in the adjuvant-induced arthritis model.

Potency of AZ11657312 is ~50x lower at the human P2X7 receptor [pA2 of 6.1 (794nM)], so in vitro studies using human cells or tissues would require higher concentrations.

Additional information

Publications for this compound

Find out more about this compound by reading related publications:

The Journal of Pharmacology and Experimental Therapeutics

Characterization of N-(Adamantan-1-ylmethyl)-5-[(3R-amino-pyrrolidin-1-yl)methyl]-2-chloro-benzamide, a P2X7 Antagonist in Animal Models of Pain and Inflammation

Gene information from the NCBi

This compound works on the following genes: