AZD 9272 is a brain penetrantmGluR5antagonist.

AZD 9272 causes a concentration dependent decrease in the magnitude of the intracellular Ca²⁺response to 1.5 μM of the mGluR group I selective agonist DHPG in both the human and the rat mGluR5 expressing cell lines. The maximal inhibition is 100%. The mean IC₅₀(±SD) value at the human mGluR5 is 7.6±1.1 nM (n=13) for AZD9272. The mean IC₅₀value at the rat mGluR5 is 2.6±0.3 nM (n=3) for AZD9272. In contrast, 10 μM of AZD9272 does not diminish the response to 10 μM ATP in the background GHEK cells. Increasing concentrations of AZD9272 causes a decrease in the potency and the maximal response of DHPG. AZD9272 completely reverses the glutamate-stimulated (EC₈₀, 80 μM) phosphatidyl inositol hydrolysis in human mGluR5-GHEK cells in a concentration-dependent manner, with IC₅₀of 26±3 nM (n=21)^[1].

The clearance of AZD 9272 is low following a single intravenous dose at 3 μmol/kg and AZD 9272 is eliminated from plasma with terminal half-lives between 2 and 6 h. The terminal half-lives following oral dosing are similar to the half-lives following intravenous dosing. The volume of distribution at steady state is intermediate for AZD9272^[1]. AZD9272 causes no cocaine-appropriate responding and causes a non-dose-dependent reduction in response rates at higher doses. AZD9272 at 2.84 mg/kg causes greater than 80% and typically more than 99% MTEP-appropriate responding up to 20 hours after dose, with a decline to approximately 20% at 24 hours after dose, yielding a t_1/2of 21.93 hours, and causes no systematic effects on response rates. The first time point at which AZD9272 causes >90% MTEP-appropriate responding is at 30 minutes after dose^[2].

284.22

C₁₄H₆F₂N₄O

327056-26-8

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