TPMPA (hydrate)

TPMPA is a GABA_A-Ρ1 (Ρ1 GABA_C) receptor antagonist that is 8-fold selective for GABA_A-Ρ1 over GABA_A-Ρ2 (Ρ2 GABA_C) receptors expressed in X. laevis oocytes (K_bs = 2 and 16 μM, respectively).¹ In rat hippocampal slices, TPMPA blocks the inhibitory effect of the GABA_B agonist 3-APMPA on excitatory postsynaptic currents (EPSCs) with an EC₅₀ value of 490 μM.² TPMPA (100 μM) increases light sensitivity and the maximal response of rat retinal ganglion cells without altering their dynamic range.³ In sleeping rats, TPMPA (50 μg, i.c.v.) increases waking from 45 to 62% compared to a vehicle control and decreases slow-wave and paradoxical sleep (REM) by 11 and 5.4%, respectively.⁴

1.Chebib, M., Mewett, K.N., and Johnston, G.A.GABAC receptor antagonists differentiate between human Ρ1 and Ρ2 receptors expressed in Xenopus oocytesEur. J. Pharmacol.357(2-3)227-234(1998) 2.Ragozzino, D., Woodward, R.M., Murata, Y., et al.Design and in vitro pharmacology of a selective γ-aminobutyric acidC receptor antagonistMol. Pharmacol.50(4)1024-1030(1996) 3.Jensen, R.J.Blocking GABAC receptors increases light responsiveness of retinal ganglion cells in a rat model of retinitis pigmentosaExp. Eye Res.10521-26(2012) 4.Arnaud, C., Gauthier, P., and Gottesmann, C.Study of a GABAC receptor antagonist on sleep-waking behavior in ratsPsychopharmacology (Berl)154(4)415-419(2001)