A novel free fatty acid receptor 1 (GPR40/FFAR1) agonist, MR1704, enhances glucose-dependent insulin secretion and improves glucose homeostasis in rats.

Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats.

Pharmacological characterization of a novel potent, selective, and orally active phosphodiesterase 10A inhibitor, PDM-042 [()-4-(2-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-]pyrazin-2-yl)vinyl)-6-(pyrrolidin-1-yl)pyrimidin-4-yl)morpholine] in rats: potential for the treatment of schizophrenia.

Recently, we identified a novel phosphodiesterase 10A (PDE10A) inhibitor, PDM-042 (()-4-(2-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-]pyrazin-2-yl)vinyl)-6-(pyrrolidin-1-yl)pyrimidin-4-yl)morpholine). PDM-042 showed potent inhibitory activities for human and rat PDE10A with IC values of less than 1 nmol/L and more than 1000-fold selectivity against other phosphodiesterases. Tritiated PDM-042, [H]PDM-042, had high affinity for membranes prepared from rat striatum with a value of 8.

Eicosapentaenoic acid attenuates statin-induced ER stress and toxicity in myoblast.

We previously reported that eicosapentaenoic acid (EPA) improved statin-induced rhabdomyolysis in rats (Naba et al. [6]). In this study, we report for the first time direct improvement by EPA of statin-induced toxicity in cultured myoblasts and the mechanistic involvement of endoplasmic reticulum (ER) stress.

Pharmacological profiles of the novel analgesic M58996 in rat models of persistent and neuropathic pain.

We investigated the effects of 4-(N-{1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}-N-methylamino)benzoic acid monohydrochloride (M58996), a novel analgesic, on persistent and neuropathic pain in rats. In the formalin test, oral M58996 (0.3 - 10 mg/kg) reduced nociceptive behaviors only in the late phase.

Improving effect of ethyl eicosapentanoate on statin-induced rhabdomyolysis in Eisai hyperbilirubinemic rats.

The effect of ethyl eicosapentanoate (EPA-E) on statin-induced rhabdomyolysis was investigated by co-administration of EPA-E and pravastatin (PV), as a typical statin, to Eisai hyperbilirubinemic rats (EHBR). It was confirmed that the plasma PV concentration was not affected by simultaneous administration of EPA-E, and there was no cumulative increase of PV during prolonged co-administration of EPA-E and PV. Muscular degeneration was prominent (incidence 5/5; average grade 3.