Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), that in combination with carbidopa and levodopa used for the treatment of Parkinson's disease. Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD). When entacapone is given in conjunction with levodopa and carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and carbidopa alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson’s disease. The higher levodopa levels may also lead to increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. When 200 mg entacapone is coadministered with levodopa/carbidopa, it increases levodopa plasma exposure (AUC) by 35-40% and prolongs its elimination half-life in Parkinson’s disease patients from 1.3 to 2.4 hours. Plasma levels of the major COMT-mediated dopamine metabolite, 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD), are also markedly decreased proportionally with increasing dose of entacapone. In animals, while entacapone enters the CNS to a minimal extent, it has been shown to inhibit central COMT activity. In humans, entacapone inhibits the COMT enzyme in peripheral tissues. The effects of entacapone on central COMT activity in humans have not been studied.

Decanohydroxamic acid had almost no antibacterial activity. At 100 γ/ml, the acid showed growth inhibition on all the fungi tested except Monosporium apiospermum 213. The acid was found to have atropine-like, papaverine-like, anti-acetylcholine, and antihistamine actions, and a slight effect on blood (number of erythrocytes, leucocytes, and hemoglobin), but no marked effect was found on other factors. The action of this acid on the circulating system is mainly vasodilation and depression of the total carotid pressure, and no marked changes were produced in heart movement and cardiogram. A very slight irritation was observed as its local action, especially in an emulsified ointment on the skin, but not when the acid was used as a lipophilic ointment. Acute toxicity of the acid was very weak, the 2.5% Tween suspension giving the values of over 1430 mg/kg in mice by subcutaneous and intraperitoneal injection, over 7200 mg/kg in mice by oral administration.

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.

Pipemidic Acid is a quinolone antibacterial agent. It’s used in the treatment of urinary tract infections, recidive cystitis, prolongation of the therapy of pyelonephritis (prolonged therapy at patients with tendency to recidives. It belongs to DNA Gyrase inhibitor pharmacological group on the basis of mechanism of action and also classified in Antibacterial pharmacological group. Pipemidic acid is contraindicated at conditions of proved hypersensitivity, severe renal and hepatic insufficiency, cirrhosis of the liver, porphyria, diseases of the central nervous system (epilepsy and neurological conditions with low level for convulsions). Pipemidic acid is contraindicated at children and adolescents at growing phase.

N,N-Dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]- benzopyrano[2,3-b]pyridine-7-acetate (Y-23023/ Tilnoprofen arbamel) is a prodrug developed as a new non-steroidal anti-inflammatory drug (NSAID), by Yoshitomi and Japan Tobacco for treatment pain in Rheumatoid arthritis, but was discontinued. Y-23023 is rapidly hydrolysed to an active metabolite, alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid (TILNOPROFENIC ACID), cyclo-oxygenase inhibitor.

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-Hydroxyisovaleric acid (also known as 3-hydroxyisovaleric acid or 3HIA) is a normal human metabolite excreted in the urine. It is a byproduct of the leucine degradation pathway. Beta-Hydroxyisovaleric acid serves as a sensitive indicator of marginal biotin deficiency in humans. The variability of the proportion of leucine catabolites excreted as 3HIA suggests substantial population heterogeneity in the metabolic capacity of the 3HIA-carnitine detoxification pathway. In addition, was shown that in type II diabetic patients the catabolism of leucine was accelerated even in the absence of ketosis and that the urinary beta-hydroxyisovaleric acid concentration was a useful marker of short-term metabolic control in these patients.

Hydroxynaphthoic acid is a salt part of discontinued drug Bephenium hydroxynaphthoate. It was also shown to have anti-diabetic effect in mice, acting as a chemical chaperone and reducing ER stress.