THE INFLUENCE OF 3-PHTHALYMIDOACYLOXY-1,2-DIHYDRO-3H-1,4-BENZODIAZEPIN-2-ONES ON RATS APPETITE AND WEIGHT BY "ANOREXIA" METHOD

Abstract

In recent years, the problem of the regulation of feeding behavior has attracted attention due to the global obesity in the world. It is known that for the last 25 years the number of people suffering from obesity has increased threefold. Therefore, the search for new chemical compounds and development on their basis of drugs that regulate appetite and body weight is an actual problem of Experimental and Clinical Pharmacology. Therefore, the aim of this work is to find safe and highly effective compounds of reducing the appetite and body weight in a series of 3-phtalymidoacyloxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones by "Anorexia" method in experiments on rats in comparison with the hormone leptin. For the first time in a series of 3-phtalymidoacyloxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (1-8) compounds anorexic activity that reduces the appetite of rats under the influence of the compounds at low doses (0.164-0.193 μM) in comparison with the control and satiety hormone leptin (20 nM) was found. One of the investigated compounds (6) demonstrates high anorexic effect with ED50 0.134 μM. As to its effect the found compound is similar to the action of the hormone leptin. It is shown that increasing the length of phtalymidoaminoacid fragment via ethylene glycol residue in the third position of benzodiazepines nucleus leads to an increase of anorexic activity. Thus, our studies have shown that in a series of 3-phtalymidoacyloxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones there are substances with high anorexic activity. They are of interest for further investigation as potential drugs regulating eating behavior and reducing the appetite and body weight.