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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.
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1. Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorg. Med. Chem. Lett. 22(18), 5903-5908 (2012).
2. The novel phosphodiesterase 10A inhibitor THPP-