Identification of phosphodiesterase 10A (PDE10A) was first reported in mice and humans at the same period from three laboratories (Soderling et al. 1999; Fujishige et al. 1999a; Loughney et al. 1999). Primary sequence of PDE10A possesses a catalytic domain (HD domain) conserved within the 3, 5′-cyclic nucleotide phosphodiesterase family. PDE10A shows substrate specificity for both cyclic AMP (cAMP) and cyclic GMP (cGMP), and hydrolyzes these molecules to 5′-AMP and 5′-GMP, respectively. PDE10A mRNA and protein are highly expressed in the brain, particularly, in the striatal medium spiny neurons (Fujishige et al. 1999b; Seeger et al. 2003). Genetic deletion of PDE10A gene in mice as well as PDE10A inhibition by papaverine, a first reported PDE10 inhibitor, showed altered behavioral responses to several schizophrenia models (Siuciak et al. 2006; Siuciak et al. 2008); therefore, therapeutic implications of PDE10A inhibitor for psychiatric...
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