Propatylnitrate (or propatyl nitrate), a coronary vasodilator that has been studied for the relief of acute attacks of angina pectoris. However, was revealed that this drug didn’t abolish or diminish the frequency of attacks of angina pectoris.

Fendiline or Sensit (N-(3,3-diphenylpropyl)-(1-phenylethyl)-amine), is a diphenylalkylamine blocker of L-type calcium channels. Fendiline is an anti-anginal agent for the treatment of coronary heart disease. Pharmaco-dynamically, it exerts the typical calcium as well as calmodulin antagonistic actions: inhibition of the transmembrane calcium current, smooth muscle relaxation, negative inotropism, cardioprotection, inhibition of calmodulin-activated myosin light-chain kinase and phosphodiesterase. Pharmacokinetics reveal slow onset of action and a long half-life. The anti-anginal and anti-ischaemic efficacy of fendiline has been proven in several placebo-controlled, double-blind trials. Fendiline is an FDA-approved, albeit now clinically obsolete. Additionally, fendiline is a specific inhibitor of K-Ras plasma membrane localization that also inhibits K-Ras signal output and blocks the proliferation of K-Ras-transformed tumor cells.

Gepefrine (Pressionorm and Wintonin) is an antihypotensive agent. It was used for therapy of orthostatic dysregulation. One hour after oral administration of 30 mg or 45 mg gepefrine the blood pressure increased significantly at rest and more markedly on standing and during the step test. Gepefrine led to a reduction in pathological orthostatic regulation during the early phase as well as to the prevention of subjective and objective signs of orthostatic adjustment disorder during the late phase. Patients with insufficient rise in blood pressure during the step test (80 watts) showed after gepefrine a distinct tendency towards normalisation and the regression of subjective states of exhaustion. Gepefrine caused on average no substantive alternations in heart rate during all phases of the investigation. Complications or side-effects due to the method or the medicament were not observed.

Norfenefrine or meta-octopamine, also known as 3,β-dihydroxyphenethylamine, is an adrenergic agent used as a sympathomimetic drug which is marketed in Europe, Japan, and Mexico. Along with its structural isomer p-octopamine and the tyramines, norfenefrine is a naturally occurring, endogenous trace amine and plays a role as a minor neurotransmitter in the brain. Norfenefrine controls blood pressure in acute hypotensive states eg pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesth, MI, septicemia, blood transfusion and drug reactions. Adjunct in treatment of cardiac arrest and hypotension.

Tedisamil is an antiarrhythmic with additional anti-ischaemic properties, which acts via potassium channel blockade. This drug can be categorised as a class III antiarrhythmic agent due to its effects of action potential and QT interval prolongation in these patients. Although tedisamil has been shown to be an effective anti-ischaemic agent, with Phase III trials for angina pectoris now completed, the company are now pursuing the use of tedisamil for the treatment of atrial fibrillation, for which tedisamil is still in Phase II/III clinical trials. The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted not to recommend approval for Solvay Pharmaceuticals’ investigational anti-arrhythmic drug Pulzium (Tedisamil) and asked the company to give the FDA more information.

Remikiren (Ro 42-5892) is a very potent renin inhibitor in vitro and in vivo. Clinical results show that remikiren is a potent orally active renin inhibitor inducing a long lasting blood pressure decrease. Remikiren development has been discontinued.

Epanolol has been shown in animal models to be a selective beta-adrenoceptor partial agonist with agonist activity about 20 to 25% of that of the full agonist isoprenaline. Epanolol is a once-daily agent for the treatment of angina pectoris. The pharmacodynamic consequences in man of the degree of agonist activity possessed by the beta 1-selective partial agonist epanolol include little reductions at rest in heart rate, blood pressure, various measures of cardiac haemodynamic parameters, peripheral blood flow and renal function. On exercise there is attenuation of the heart rate and systolic blood pressure responses, with less perceived exertion than with atenolol. The lack of significant accumulation of epanolol indicates that no alteration of dose is necessary when using epanolol in elderly patients with normal renal and hepatic function.

Acadesine, also known as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, AICA-riboside, and AICAR, is an AMP-activated protein kinase activator which is used for the treatment of acute lymphoblastic leukemia (ALL) and may have applications in treating other disorders such as mantle cell lymphoma (MCL). The mechanism by which acadesine selectively kills B-cells is not yet fully elucidated. The action of acadesine does not require the tumour suppressor protein p53 like other treatments. This is important, as p53 is often missing or defective in cancerous B-cells. Studies have shown acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Antiapoptotic proteins of the Bcl-2 family regulate MCL cell sensitivity to acadesine and combination of this agent with Bcl-2 inhibitors might be an interesting therapeutic option to treat MCL patients. Acadesine has anti-ischemic properties that is currently being studied (Phase 3) for the prevention of adverse cardiovascular outcomes in patients undergoing coronary artery bypass graft (CABG) surgery. Adenosine itself has many beneficial cardioprotective properties that may therefore be harnessed by this new class of drugs. Unlike adenosine, acadesine acts specifically at sites of ischemia and is therefore void of the systemic hemodynamic effects that may complicate adenosine therapy. Animal and in vitro studies have established acadesine as a promising new agent for attenuating ischemic and reperfusion damage to the myocardium. Acadesine also possesses the theoretical (but unproven) benefit of attenuating reperfusion injury after acute myocardial infarction (MI). Further research is needed to define the full potential of this unique agent in various clinical situations involving myocardial ischemia.

Picodralazine is a peripheral vasodilator, sympatholytic agent exerting antihypertensive properties.

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.