Acetyldigoxin, a cardiac glycoside that has been studied in patients with congestive heart failure.

Tiazotic acid is an antioxidant. As tiazotic acid morpholinium salt it is marketed under the brand names Thiotriazoline, Tiokor among others in Russia, Ukraine, Uzbekistan as the treatment of ischemic heart diseases. It is proposed to be a hepatoprotective, wound-healing and antiviral agent. A comparative international multicenter randomized trial, assessed anti-anginal anti ischemic efficacy and safety of Trimetazidine (60 mg/d) and Thiotriazoline (600 mg/d) in symptomatic patients with chronic ischemic heart disease receiving the first line therapy. The study assessed the efficacy of the two drugs on total exercise duration, time to 1-mm ST segment depression, the number of angina attacks and nitroglycerin tablets consumed amount. Both drugs have demonstrated clinical efficacy equal for all primary and secondary endpoints. Thiotriazoline was also used for the he correction of hepatotoxicity during combined chemoradiotherapy for cancer patients.

Hidrosmin, a synthetic bioflavonoid, is a phlebotonic (capillary stabilising agent). It is marketed under the brand name Venosmil among others. Venosmil is a medicinal product indicated for: short-term (2-3 months) relief from oedema and symptoms related to chronic venous insufficiency in adults. Although the mechanism of action of hidrosmin has not been fully elucidated, it could be related toinhibition of the degradation of catecholamines, specifically inhibition of catechol-O-methyltransferase. Although the exact mechanism of action is unknown, hidrosmin has four main pharmacological actions: 1.It reduces the capillary permeability induced by various agents such as histamine, bradykinin, etc. and reduces the capillary fragility induced by a deficiency diet. 2.It increases the deformability of red blood cells and the viscosity of the blood. 3.It induces the contraction of smooth muscle in the vein wall in a gradual and sustained manner. 4.It produces dilation of the lymphatic collectors and increases the rate of lymphatic conduction, thereby improving lymphatic flow. The efficacy of Venosmil was evaluated in two clinical trials in a total of 70 patients with acute and chronic venous disease, who were treated with 200 mg hidrosmin orally three times per day and/or 2 g hidrosmin topically (gel) two or three times per day for one and two months Hidrosmin was effective at reducing oedema, ulcers and varicose eczema. Venosmil therefore possesses intrinsic activity against the consequences of venous stasis secondary to varicose dilation of the veins in the lower limbs, producing an improvement in the clinical symptoms of peripheral venous insufficiency (pain, heaviness, oedema, etc.) that is significantly different to that produced by placebo.

Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. In addition it inhibits prostaglandin biosynthesis. Well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding.

Beta-acetyldigoxin (under the brand name Novodigal), a beta-acetyl derivative of digoxin, acts as a prodrug. It is deacetylated in the cells of the intestinal mucosa and is present inside the body solely in the form of digoxin. β-acetyldigoxin has a higher bioavailability than digoxin. Beta-acetyldigoxin is a substrate of P-glycoprotein.

Heptaminol is an amino alcohol that has been used as a myocardial stimulant and vasodilator and to relieve bronchospasm. Its most common therapeutic use is in orthostatic hypotension. The mechanism of heptaminol's therapeutic actions is not well understood although it has been suggested to affect catecholamine release or calcium metabolism.

Buthiazide (or Butizide) is a diuretic of the thiazide class. It was used for the treatment of mild to moderate essential hypertension. Buthiazide reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.

Dimetofrine is a selective agonist of post-synaptic a1-adrenergic receptors. The drug was investigated as a cardiostimulant to treat orthostatic hypotension. Clinical investigation showed that dimetofrine relieves asthenia, paleness, drowsiness, fatigue, headache and other symptoms associated with hypotension. It was observed, that in acidic conditions similar to conditions in the stomach, dimetofrine is able to react with nitrites with the formation of highly mutagenic compound 2,6-dimethoxy-1,4-benzoquinone (DMBQ).

Practolol is a beta-adrenergic antagonist that has been used in the emergency treatment of cardiac arrhythmias. Practolol is a cardio-selective beta-blocking agent with an intrinsic sympathomimetic action, but devoid of local anaesthetic effect. It has been found effective in post infarction arrhythmias. In early infarction it reduces the area of necrosis as measured by surface ST segment mapping. Practolol has also been shown to be an effective drug in treating angina. Long-term treatment revealed advantageous effects of practolol on the incidence of anginal attacks and the number of nitroglycerin tablets consumed in daily life. There was also a noticeable improvement in the ECG. The results obtained in a double-blind trial, with placebo, proved the effectiveness of the drug. The treatment enabled the patients to lead appreciably more active lives. A marked increase in work performance, depending on the dose applied, was confirmed in exercise tolerance tests. No side-effects which would call for discontinuance of the treatment were seen during long-term administration with doses up to 800 mg daily. Like other beta-adrenergic antagonists, practolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Practolol binds at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure. Practolol, discovered in 1966, was removed from the market due to severe side effects including conjunctival scarring, fibrosis, and metaplasia.

Tribenoside, a glucofuranoside derivative has been shown to have potent anti-allergic and anti-inflammatory properties. It has been reported to display a pluripotent antagonistic action against histamine, serotonin, bradykinin and other inflammatory substances. Tribenoside decrease capillary permeability, thus reducing edema. Tribenoside combat the pathological processes of capillaries and veins. It is used in adults and adolescents for treatment of venous circulation diseases. Although Tribenoside is derived from a sugar substance, it doesn’t affect the carbohydrate metabolism even in diabetics. Tribenoside might cause some side effects such as skin redness, headache. Very rare cases are: systemic anaphylaxis, including urticaria, angioedema.