Trapidil, a platelet-derived growth factor antagonist, was originally developed as a vasodilator and anti-platelet agent and has been used to treat patients with ischemic coronary heart, liver, and kidney disease. Used to treat patients with ischemic coronary heart, liver, and kidney disease.

Levosimendan (Simdax) is a novel intravenous agent that exerts inotropic effects through sensitization of myofilaments to calcium and vasodilator effects by binding to cardiac troponin C in a calcium-dependent manner. It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation. Unlike other calcium sensitizing compounds, the binding of levosimendan is highly dependent on the intracellular concentration of calcium, such that calcium sensitivity is enhanced only when the calcium level is elevated. Levosimendan is licensed for the treatment of decompensated heart failure in many countries but not in North America. This drug also passed phase III clinical trials for the prevention of low cardiac output syndrome in pediatric patients after open heart surgery.

Benziodarone is a coronary dilatator drug. Benziodarone in therapeutic dosage has no effect on blood coagulation and does not alter the prothrombin level. Bleeding complications occurred, when benziodarone is given to patients receiving anticoagulant therapy with warfarin sodium. Jaundice might occurred from 8 to 16 weeks after the beginning of the treatment with Benziodarone. Combination of Flecainide with Benziodarone should be avoided or used only with strict monitoring. Benzbromarone is an other benzofuran derivative acting as anuricosuric agent by reducing the proximal tubular reabsorption of uric acid. The hypouricaemic action of benziodarone (Amplivex-Labaz) is prompt. The maximum drop of uricaemia after Amplivex administration (2 tablets/day) occurs during the first three days. The uric acid level declines by as much as 80% of the baseline value. For long-term treatment 1 tablet per day is sufficient, in some instances even 1 tablet twice a week. The tolerance of the preparation is satisfactory.

Vernakalant is a new antiarrhythmic drug that acts selectively in the atrium, targeting atrial specific channels. Vernakalant is an anti-arrhythmic medicine that acts preferentially in the atria by prolonging atrial refractoriness and by rate-dependently slowing impulse conduction. These anti-fibrillatory actions on refractoriness and conduction are thought to suppress reentry, and are potentiated in the atria during atrial fibrillation. The preferential effects of vernakalant on the atria are postulated to result from its block of currents that are expressed in the atria (e.g., the ultra-rapid delayed rectifier potassium current; and the acetylcholine-activated potassium current), but not in the ventricles, as well as the unique electrophysiologic condition of the fibrillating atria. An oral formulation of vernakalant is in phase II development as a long-term maintenance therapy for patients with atrial fibrillation. An intravenous formulation of vernakalant has been launched in most countries in Europe and Latin America, and in Hong Kong, for the acute conversion of atrial fibrillation. The product has been approved for the acute conversion of atrial fibrillation in South Africa, Iceland, Turkey and is awaiting approval for the same indication in Canada. Phase III development of the IV formulation is ongoing at sites in Asia, and development is currently on hold in the US.

Cibenzoline is a class I sodium channel blocker antiarrhythmic drug available in a limited number of countries. Cibenzoline also has moderate calcium channel blocking (class IV) effects and prolongs the action potential duration through its potassium channel blocking (class III) effect. It is used for the treatment of supraventricular and ventricular arrhythmias, and in obstructive hypertrophic cardiomyopathy.

Proscillaridin is a substance that was used in Europe for the treatment of heart failure and atrial fibrillation. Proscillaridin belongs to glycosides and acts as a Na /K -ATPase inhibitor.

Hexobendine (Ustimon or ST7090) is a vasodilator. It inhibits uptake of adenosine and cAMP. Hexobendine was investigated in clinical trials for the treatment of cerebrovascular and coronary artery diseases.

Bucladesine is a cyclic nucleotide derivative which mimics the action of endogenous cAMP and is a phosphodiesterase inhibitor. The compound is used in a wide variety of research applications because it mimics cAMP and can induce normal physiological responses when added to cells in experimental conditions. cAMP is only able to elicit minimal responses in these situations. The neurite outgrowth instigated by bucladesine in cell cultures has been shown to be enhanced by nardosinone. Recently, the effect of bucladesine as a cAMP analog has been studied on the pentylenetetrazol-induced seizure in the wild-type mice. The data showed that bucladesine (300nM/mouse) reduced the seizure latency and threshold. In addition they found that combination of bucladesine and pentoxyfillin has additive effect on seizure latency and threshold. Bucladesine is more lipophilic than cAMP and in contrast to cAMP capable of penetrating cell membranes. Bucladesine interferes with different protein kinases which are normally activated by cAMP. Bucladesine has undergone in the past clinical developments as systemic treatment for cardioprotection and as topical treatment to improve wound healing. In Japan, a bucladesine ointment (Actosin® ointment; Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan) was marketed to treat skin ulcers. Clinical studies have shown favourable effects on diabetic foot ulcers or decubitus, but the compound was later withdrawn despite good tolerability. One possible reason for the withdrawal may be the odour of the cream formulation which can be related to the hydrolytic cleavage in aqueous solutions resulting in release of butyric acid.

Nicorandil is a derivative of the niacinamide that is structurally combined with an organic nitrate. It provides a dual mode of action leading to relaxation of vascular smooth muscle. Nicorandil is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase. Nicorandil has a direct effect on coronary arteries without leading to a steal phenomenon. The overall action improves blood flow to post-stenotic regions and the oxygen balance in the myocardium.