ADX71743

ADX71743 is a highly selective, noncompetitive and brain-penetrant metabotropic glutamate receptor 7 negative allosteric modulator (mGlu7 NAM). ADX71743 can cross the blood-brain barrier (BBB) and possesses anxiolytic activity.^[1][2]. In Vitro:ADX71743 has an IC₅₀ of 300 nM in-house cell lines. Pretreatment of ADX71743 (3 μM; for 20 min) before high-frequency stimulation (HFS) results in an almost complete blockade of LTP induction^[1].
ADX71743 (0.1, 10 μM) reverses L-AP4-induced depression of synaptic transmission and results in a concentration-dependent reversal of the L-AP4-induced depression. 0.1 μM ADX71743 reverses the effects of L-AP4 by 11% and 10 μM results in a 20% reversal^[2].
ADX71743 can against an EC₈₀ of glutamate (IC₅₀ of 22 nM) as well as against an EC₈₀ of L-AP4 (IC₅₀ of 125 nM)^[2].
In Vivo:ADX71743 (50, 100, 150 mg/kg; SC) results in robust reductions in numbers of buried marbles to near maximal levels at lower doses (50 and 100 mg/kg)^[2].
ADX71743 (12.5, 100 mg/kg for mice and 100 mg/kg for rat; SC) has a T_1/2 of 0.68, 0.40 hours, a C_max of 1380, 12766 ng/ml of 12.5 mg/kg and 100 mg/kg in mice^[2].
ADX71743 (12.5 and 100 mg/kg, subcutaneous injection, single dose) demonstrates bioavailability in C57Bl6/J mice, penetrates the blood-brain barrier (CSF/plasma concentration ratio was 5.3% at Cmax), shows linear increases in plasma exposure with increasing dose, and is cleared rapidly (half-life approximately 0.5 hours); similar pharmacokinetic characteristics are observed in Sprague-Dawley rats (100 mg/kg, subcutaneous injection, single dose), with a plasma C_max of 16800 ng/ml and a half-life of 1.5 hours^[3].