Antipsychotic-like effects of a novel phosphodiesterase 10A inhibitor T-251 in rodents.

Phosphodiesterase 10A (PDE10A) is a dual-substrate PDE that hydrolyzes both cAMP and cGMP. PDE10A is selectively expressed in medium spiny neurons in the striatum, suggesting the potential of PDE10A inhibitors in the treatment of schizophrenia. This study presents the pharmacological profile of a novel PDE10A inhibitor, 2-[(E)-2-(7-fluoro-3-methylquinoxalin-2-yl)vinyl]-6-pyrrolidin-1-yl-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-4-amine hydrochloride (T-251) in rodent models of schizophrenia.

Long-lasting anti-emetic effect of T-2328, a novel NK(1) antagonist.

The effect of T-2328 {2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride}, a novel tachykinin NK(1)-receptor antagonist, was examined on cisplatin-induced emesis in ferrets. Cisplatin induced acute emesis in 24 h and delayed emesis during 24 and 72 h, respectively. Ondansetron, a 5-HT(3) antagonist, almost completely blocked the acute emesis and transiently reduced the delayed emesis.

Pharmacological characterization of T-2328, 2-fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile dihydrochloride, as a brain-penetrating antagonist of tachykinin NK1 receptor.

The pharmacological properties of T-2328 were evaluated as an antagonist of the tachykinin neurokinin 1 (NK(1)) receptor. T-2328 inhibited the specific binding of [(3)H][Sar(9),Met(O(2))(11)]substance P to tachykinin NK(1) receptors in human lymphoblastic IM9 cells with K(i) of 0.08 nM.