THPP-1 is an inhibitor of phosphodiesterase 10A (PDE10A; Ki = 1 nM).1 It is selective for PDE10A over PDE1A-9A and PDE11A (Kis = 44->50,000 nM for all). THPP-1 (3 mg/kg) decreases the number of avoidances in the conditioned avoidance response test in rats and reduces MK-801-induced increases in locomotor activity in mice.2 It improves novel object recognition in rats when administered at doses of 0.3 and 1 mg/kg.
1.Raheem, I.T., Breslin, M.J., Fandozzi, C., et al.Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophreniaBioorg. Med. Chem. Lett.22(18)5903-5908(2012) 2.Smith, S.M., Uslaner, J.M., Cox, C.D., et al.The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkeyNeuropharmacology64215-223(2013)