AM-1488

AM-1488 is a potent, orally active glycine receptor (GlyR) potentiator (hGlyRα3 EC50=0.45 μM)[1][2].

Signaling Pathways >> Others >> Others

Research Areas >> Neurological Disease

AM-1488 also potentiates native GlyRs in mouse spinal-cord neurons, which express mostly GlyRα1(β) and GlyRα3(β)[1]. Cell Viability Assay[1] Cell Line: Mouse spinal-cord neuron Concentration: 0.5 μM Incubation Time: 10 min Result: Increased the peak current evoked by a puff of 20 µM glycine in five out of five cells, from an average of 50.8 pA to an average of 222.2 pA.

AM-1488 (oral gavage; 20 mg/kg; once) treatment significantly reverse mechanical allodynia induced by nerve injury in a mouse model of neuropathic pain, without being confounded by sedation or motor side effects[1]. Animal Model: Mouse model of spared nerve injury (SNI)[1] Dosage: 20 mg/kg Administration: Oral gavage; 20 mg/kg; once Result: Produced a significant 94% reversal of tactile allodynia, and the unbound brain concentration was 2.8- and 1.6-fold higher than the mouse GlyRα1 and GlyRα3 EC50 values, respectively. Animal Model: Naive mice[1] Dosage: 20 mg/kg Administration: Oral gavage; 20 mg/kg; once Result: Showed not significantly different from mice treated with vehicle.

[1]. Xin Huang, et al. Crystal structures of human glycine receptor α3 bound to a novel class of analgesic potentiators. Nat Struct Mol Biol. 2017 Feb;24(2):108-113.

[2]. Howard Bregman, et al. The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors. J Med Chem. 2017 Feb 9;60(3):1105-1125.