Palosuran, also known as ACT-058362, a potent and specific antagonist of the human UT receptor. Urotensin inhibition with palosuran was a promising alternative in pulmonary arterial hypertension. Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues. Palosuran improves pancreatic and renal function in diabetic rats. Phase-II clinical trials for diabetic nephropathies and cardiovascular disorders were discontinued.

Pipratecol is substituted thienoimidazole. It is the H+/K(+)-ATPase inhibitor. In a high concentration of 10(-4) g/ml, pipratecol increased the amplitude of isolated guinea-pig atrial contractions while decreased the rate. But, in a low concentration of 10(-8) g/ml, the drug decrease the amplitude and increased the rate slightly. The effects of adrenaline and noradrenaline were suppressed by the preceding addition of pipratecol, while that of isoproterenol was scarcely. The effect of pipratecol on atrial contractions was hardly influenced by reserpine with which the animal had been pretreated 24 hours before the sacrifice of animal. The augmentative effect of nicotine on atrial contractions was slightly suppressed by the preceding addition of pipratecol. From these results, it was assumed that pipratecol has some affinity with the adrenergic receptor of atria. As a peripheral vasodilator it has been used in conjunction with raubasine in the treatment of cerebrovascular disorders. Pipratecol was used as antiulcerative agent also.

Abitesartan is an angiotensin II receptor antagonist, antihypertensive (non-peptidic) agent.

Mazokalim is a potassium channel agonist. It was studied in the treatment of asthma and hypertension.

Ataciguat is a novel anthranilic acid derivative that belongs to a new structural class of sGC activators which are capable of activating the oxidized form of sGC. Ataciguat, a nitric oxide-independent soluble guanylate cyclase activator, is being developed by Sanofi (previously sanofi-aventis), in collaboration with Mayo Clinic and National Center for Advancing Translational Sciences. Ataciguat is in phase II clinical trials for the treatment of aortic valve stenosis. It had been used to treat neuropathic pain and peripheral arterial disease, but this research has been discontinued.

Naminidil, a potassium channel opener, was under development with Bristol-Myers Squibb as a topical treatment for androgenetic alopecia. The research has been discontinued.

Trixolane is a spasmolytic, vasodilator, choleretic agent.

Arfalasin or Hoe 409, an angiotensin II (AII) blocker, inhibits the renin release thus delay recovery of urinary osmolality.

Teprotide, a nonapeptide isolated from the venom of a Brazilian pit viper, Bothrops jararaca, was the first angiotensin converting enzyme (ACE) inhibitor to be discovered and tested. It was found to be an effective, non-toxic antihypertensive agent as well as an afterload-reducing agent for patients with congestive heart failure (CHF). The primary activity of teprotide resulted from blockade of the angiotensin I converting enzyme--the pivotal step in the renin-angiotensin-aldosterone system (RAAS), and consequent reductions in angiotensin II levels. There was limited clinical testing for teprotide because of: its scarcity; the need for parenteral administration; and the subsequent discovery and synthesis of captopril, the first orally active angiotensin converting enzyme inhibitor.

Ralinepag is a cyclohexyl amide derivative patented by Arena Pharmaceuticals, Inc. as agonists of the human prostacyclin (PGI2) receptor useful for the treatment of pulmonary arterial hypertension. Ralinepag shows selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30-50-fold selectivity over the EP3 receptor. Ralinepag had an excellent PK profile across species. Enterohepatic recirculation most probably contributes to a concentration-time profile after oral administration in the cynomolgus monkey that showed a very low peak-to-trough ratio. Phase III clinical trial is currently ongoing.