Further investigation of the neural mechanisms of mGlu5 receptor antagonists and comparisons of the mechanisms with those of ketamine may warrant the clinical efficacy of mGlu5 receptor antagonists for the treatment of depression and anxiety

disorders. “
“Chronotherapy is a pharmacologic approach whereby a drug is given at a time that varies according to physiologic needs. Our previous study using stroke-prone spontaneously hypertensive rats (SHR-SP) showed that blood pressure (BP)-lowering effect of valsartan [an angiotensin-II Selleckchem Galunisertib receptor blocker (ARB)] was longer after dosing at an inactive period than after dosing at an active period and, consequently, the survival period of the animals was longer after dosing at an inactive period (1). However, such effects based on the time of dosing were not observed for another ARB, olmesartan in this animal study. Duration of BP-lowering effect in SHR-SP and prolongation of their survival period after dosing CP-868596 molecular weight olmesartan at an active period were similar to those after dosing the drug at an inactive period (1). These animal data led us to speculate that the chronotherapeutic effects

of valsartan were different from those of olmesartan in hypertensive patients. There are precedents for chronotherapy in hypertension in clinical practice. For example, Hermida et al. reported that, in untreated hypertensive patients with a non-dipper BP pattern, a dipper BP pattern was obtained in 24% and 75% of patients after dosing of valsartan in the morning and evening, respectively (2). MRIP Recent advances in ambulatory blood pressure monitoring (ABPM) have demonstrated that a higher night-time BP and a non-dipper BP pattern are good predictors of cardiovascular events (3) and (4) and progression of renal disease (5) and (6). Cardiovascular

morbidity and mortality are also reported to elevate in hypertensive patients with a non-dipper BP pattern even under antihypertensive drugs (7). These data suggest that it is important for changing a non-dipper to dipper BP pattern in hypertensive patients. Previous studies showed that switching dosing-time of antihypertensive drugs for morning to evening in patients with a non-dipper BP pattern during morning treatment caused more BP reduction at night-time and increased a number of dipper BP pattern (8), (9) and (10). Valsartan is one of ARBs, which are frequently prescribed for the treatment of hypertension and improve the prognosis of patients. However, a non-dipper BP pattern is detected in half (46∼58%) of hypertensive patients after dosing of valsartan in the morning (11) and (12), and therefore, a chronotherapeutic approach might provide a benefit for these patients.