THPP-1

THPP-1 is a potent, selective, and orally bioavailable small molecule inhibitor of **phosphodiesterase 10A** (PDE10A), exhibiting nanomolar inhibition potency (Ki ≈ 1 nM in human and 1.3 nM in rat)[1][2][4][7]. PDE10A is an enzyme highly expressed in the brain, especially in regions involved in cognition and psychosis, where it regulates intracellular levels of cyclic nucleotides cAMP and cGMP. By inhibiting PDE10A, THPP-1 increases phosphorylation of proteins linked to synaptic plasticity and has been shown to attenuate behavioral and cognitive deficits in animal models predictive of antipsychotic and cognition-enhancing effects[1][10]. In preclinical studies, THPP-1 reverses cognitive impairments, normalizes hyperdopaminergic states, and improves memory in rodent and nonhuman primate models relevant to schizophrenia and associated cognitive dysfunction[1][10].

Other names

2-(6-chloropyridin-3-yl)-4-(2-methoxyethoxy)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl](imidazo[1,5-a]pyridin-1-yl)methanone