January - March 2008, Volume 4, Issue 1

Coman OA, Ghita I, Segarceanu A, Paunescu H, Fulga IG

Effects upon glycemia of the new phenylethylamine and pyrazol derivates of BRL35135 in rat

Acta Endo (Buc) 2008, 4 (1): 109-123
doi: 10.4183/aeb.2008.109

The beta 3 agonists have antiobesity, thermogenetic and lipolytic properties. Starting from BRL35135 structure, a well-known beta 3 agonist, 3 new phenylethylamine derivates (A, B, C) and 2 new pyrazol derivates (D, E) were synthesized.\r\nPurpose. The aim of this study was to evaluate the effect of five new compounds derived from of BRL35135 on glycemia in normal and diabetic rats.\r\nMethods. For each experiment, test and control groups of 6, 8 or 10 male Wistar rats were used. For inducing experimental diabetes mellitus, alloxan (100 mg/kg body weight) was intravenously injected. Tested substances were intraperitoneally injected (1 or 100 mg/kg body weight) and glycemia values were measured before and at 3 hours after their administration. Control groups received propyleneglycol, the solvent of the new compounds. Glycemia values were measured with a calibrated glucometer.\r\nResults. In normal rats one of the phenylethylamine compounds (substance C) (100 mg/kg body weight) had a hypoglycemic effect comparative to control (p=0.03). In glucose tolerance test, substance E (100 mg/kg body weight) stopped the increase of glycemic values determined by glucose oral administration in the first 60 minutes comparative to control (p=0.03). In the alloxanic diabetes model, before insulin administration the substances hypoglycemic effect could not be measured with the glucometer because of very high values of glycemia. After insulin administration no significant differences between the treated and the control groups were registered. Further studies on the hypoglycemic effect of substances C and E are needed in order to establish their possible antidiabetic effect.\r\nConclusion. A phenylethylamine derivate and a pyrazol derivate of BRL35135 had a hypoglycemic effect in normal rats, but this effect could not be confirmed in rats with alloxanic diabetes.

Keywords: beta 3 agonist, BRL35135, diabetes, glycemia, alloxan

Correspondence: Oana Andreia Coman, 2 Av. Ion Muntenescu Str, 71407 Bucharest, Romania, Tel ++40212304400, e-mail: andreiacoman@yahoo.com