TP-003

TP-003 is a positive allosteric modulator of the GABAA receptor (GABAAR). It potentiates GABA-induced currents in HEK293 cells expressing alpha1beta2gamma2, alpha2beta3gamma2, alpha3beta3gamma2, or alpha5beta2gamma2 subunit-containing GABAARs (EC50s = 20. 10. 3. and 5. nM, respectively). TP-003 (10 mg/kg) increases the number of entries into, and the time spent in, the open arms of the elevated plus maze in triple point-mutated mice in which only GABAARs containing the alpha2 subunit are sensitive at the benzodiazepine (BDZ) site but not in mice with wild-type GABAARs or mice expressing only alpha3-BDZ-sensitive GABAARs. It also increases locomotor activity in mice expressing only alpha2-BDZ-sensitive GABAARs when administered at a dose of 3 mg/kg but reduces locomotor activity in mice expressing only alpha1-BDZ-sensitive GABAARs at 3, 10, and 30 mg/kg. TP-003 (10 mg/kg) induces muscle relaxation in mice expressing only alpha3-BDZ-sensitive GABAARs but not those expressing alpha2-BDZ-sensitive GABAARs. InChI: InChI=1S/C23H16F3N3O/c1-23(2,30)18-7-8-29-20(12-28-22(29)21(18)26)13-3-6-19(25)17(10-13)16-5-4-15(24)9-14(16)11-27/h3-10,12,30H,1-2H3 InChIKey: SJMMDWXJSSJHOQ-UHFFFAOYSA-N SMILES: N#CC1=CC(F)=CC=C1C2=C(C=CC(C3=CN=C4N3C=CC(C(C)(O)C)=C4F)=C2)F