Quinacainol (also known as PK 10139 or RP 54272) is a quinolinemethanol derivative patented by Pharmindustrie as an antiarrhythmic agent. Quinacainol acts as a sodium channel antagonist and demonstrated both class Ia and Ic antiarrhythmic properties. Quinacainol blocked sodium currents in a concentration-dependent manner and with a potency similar to that of quinidine. Quinacainol produces a slowing of action potential conduction, consistent with a block of sodium channels, and a slight prolongation of action potential duration, consistent with a block of potassium currents.

Darusentan is an orally active, propanoic acid-based endothelin receptor antagonist (ERA) that selectively blocks endothelin-1 (ET-1) binding to the endothelin type-A (ETA) receptor. Darusentan exhibited subnanomolar binding affinity and approximately 1000-fold selectivity for the ETA receptor in binding experiments conducted in vitro under steady-state conditions. Darusentan is orally bioavailable and, when administered to humans, maximum plasma concentrations are observed within 1–2 h post dosing. The mean elimination half-life is relatively long (>15 h), which is consistent with once-daily dosing. Darusentan is primarily glucuronidated by Phase II enzymes in the liver, and the major route of elimination of Darusentan and its metabolites is via the bile. Some glucuronidated metabolites of Darusentan are also excreted in the urine. Darusentan doses up to 300 mg/day were well tolerated and associated with a manageable safety profile in patients with resistant hypertension (RHTN). The most frequently reported adverse events in Ddarusentan-treated subjects were peripheral edema (17%) and headache (11%), which were mostly mild or moderate in severity. Other commonly reported adverse events in the Darusentan treatment group were sinusitis (8%), dizziness (7%), upper respiratory tract infection (5%) and gastroenteritis (5%). In phase III clinical trial the mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg with placebo, 17/10 mm Hg with Darusentan 50 mg, 18/10 mm Hg with Darusentan 100 mg, and 18/11 mm Hg with Darusentan 300 mg. Unfortunately, phase III clinical trial evaluating Darusentan did not achieve its co-primary efficacy endpoints of achieving a change in systolic and diastolic blood pressure after 14 weeks compared to a placebo. Perhaps for this reason, shortly after the top-line results of this study became known, the sponsor announced that Darusentan would not be developed further for resistant hypertension.

Trelnarizine is a new difluorinated piperazine derivative with a structural resemblance to flunarizine and cinnarizine and possessing calcium antagonist activity. Trelnarizine belongs to the antihistaminic, vasodilator agents.

Acrihellin (D 12316) is a cardiotonic drug. It is characterized as a cardiosteroid. In isolated organ (Langendorff heart) the positive inotropic effect proved to be stronger in comparison to digoxin. Also in dogs and cats acrihellin increases the contractile force of the myocardium; especially in failing canine heart, it increases the force of contraction (strain-gauge) and velocity of pressure rise (dp/dt max). In classical glycoside test on cat (Hatcher's dose) acrihellin is more effective than digoxin and methyldigoxin on weight basis, equivalent on a molar basis. The therapeutical index of acrihellin is like that of methyldigoxin. In cats and dogs, the compound is absorbed rapidly and almost completely, especially when administered intraduodenally.

Terciprazine was developed as an antihypertensive agent that has never been marketed. Information about the current use of this drug is not available.

Gapicomine is a coronary vasodilator, developed in Poland. It has been withdrawn from the market in the countries it was used in. Gapicomine is a major component in the drug Bicordin.

Piclonidine is imidazoline derivative. Piclonidine has a relative specificity for the hypotensive action and thus indicate that the compound differs from the chemical congener clonidine which has other pharmacological effects involving several peripheral or centrally regulated autonomic functions. Unlike clonidine, this chemically related compound did not evoke hypertensive episodes or cause sedation in animals up to the oral dose of 1 mg/kg.

Libenzapril is a long-acting, small polar angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Libenzapril competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Libenzapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow. Both libenzapril and water transport was found to be significantly higher (about two- to five-fold) in six of the seven different brain regions in hypertensive rats as compared to the normotensive controls.

Zolasartan (previously known as GR 117289) is an angiotensin II (AT1) receptor antagonist that was studied for the treatment of hypertension. It was undergoing phase II clinical trials with Glaxo Wellcome in the United Kingdom before the study was discontinued.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.