Pyridobenzodiazepines: a novel class of orally active, vasopressin V2 receptor selective agonists.

Our efforts in seeking low molecular weight agonists of the antidiuretic peptide hormone arginine vasopressin (AVP) have led to the identification of the clinical candidate WAY-151932 (VNA-932). Further exploration of the structural requirements for agonist activity has provided another class of potent, orally active, non-peptidic vasopressin V2 receptor selective agonists exemplified by the 5,11-dihydro-pyrido[2,3-b][1,5]benzodiazepine as a candidate for further development.

Metabolites of the angiotensin II antagonist tasosartan: the importance of a second acidic group.

Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensin II antagonist series, a second acidic group can improve receptor binding activity but decrease in vivo activity after oral dosing.

Characterization of serotonin receptors in isolated rat intramyocardial coronary artery.

The purpose of the present study was to characterize the receptor subtypes that mediate serotonin (5-HT)-induced contraction in isolated rat intramyocardial coronary artery. In coronary artery with and without endothelium, only 5-HT and alpha-methylserotonin maleate (5-HT2 agonist) elicited equipotent concentration-dependent contractions. The EC50 values for 5-HT and alpha-methylserotonin maleate in endothelium-intact arteries were 4.

Endothelium-dependent basilar and aortic vascular responses in normotensive and coarctation hypertensive rats.

The responsiveness of acetylcholine (ACh), nitroglycerin (NG) and norepinephrine (NE) (aorta only) in both basilar arteries (BA) and thoracic aortic (TA) rings from coarctation hypertensive rats (CHR) were studied and compared to their sham-operated normotensive control rats (SNR). The effects of these agents were also evaluated in TA or BA with and without endothelium from naive normotensive rats (NNR). Blood pressure (BP) and plasma renin activity (PRA) of CHR were significantly higher than their time-matched SNR.