TPMPA (hydrate)

TPMPA is a GABAA-ρ1 (ρ1 GABAC) receptor antagonist that shows strong selectivity for GABAA-ρ1 over GABAA-ρ2 (ρ2 GABAC) receptors, being 8-fold more potent at the ρ1 subtype. For instance, in Xenopus laevis oocytes, the binding constants (Kbs) are 2 μM for ρ1 and 16 μM for ρ2.
Beyond its primary antagonistic action, TPMPA has other notable effects. In rat hippocampal slices, it blocks the inhibitory effect of the GABAB agonist 3-APMPA on excitatory postsynaptic currents (EPSCs) with an EC50 value of 490 μM.
TPMPA also influences retinal function, as demonstrated by its ability to increase light sensitivity and the maximal response of rat retinal ganglion cells at a concentration of 100 μM, without altering their dynamic range.
Furthermore, studies in sleeping rats show that TPMPA (50 μg, administered intracerebroventricularly) can increase waking time from 45% to 62% compared to a vehicle control. Correspondingly, it decreases both slow-wave and paradoxical sleep (REM) by 11% and 5.4%, respectively.