Aim. The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model. Methods. The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used. Results. The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative. Conclusions. The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

Several studies indicate that some steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the effects of progesterone and its derivatives on cardiac injury ischemia/reperfusion (I/R). Therefore, in this study, a progesterone derivative was evaluated with the objective of evaluating its activity on I/R in an ischemia-reperfusion model. In addition, molecular mechanism involved in the activity of effect induced by progesterone derivative on perfusion pressure and coronary resistance was assed using the Langendorff technique by measuring left ventricular pressure in the absence or presence of mifepristone, yohimbine, ICI 118,551, atropine, methoctramine and L-NG-nittroarginine methyl esther (L-NAME). The results showed that progesterone derivative reduced infarct size compared with progesterone and control. In addition, it was also observed that the progesterone derivative significantly decreased the perfusion pressure and coronary resistance in isolated heart. Additionally, another set of data indicate that progesterone derivative produces low left ventricular pressure in a dose-dependent manner [0.001 to 100 nM]; however, this phenomenon was significantly inhibited by methoctramine (1 nM) and L-NAME (1 nM). In conclusion, these data suggest that a cardioprotective effect of progesterone derivative is through the interaction with M 2 muscarinic and activation of nitric oxide synthase which may be responsible for the reduction in myocardial necrosis after ischemia and reperfusion.

There is scarce information about the effects of danazol and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of danazol at the cardiovascular level is very confusing. In order to clarify those phenomena in this study, a danazol derivative was synthesized with the objective of evaluating its activity on perfusion pressure and coronary resistance and comparing this phenomenon with the effect exerted by danazol. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in the absence or presence of danazol and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by danazol derivative was evaluated by measuring left ventricular pressure in the absence or presence of following compounds; flutamide, prazosin, metoprolol, indomethacin and nifedipine. The results showed that danazol derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and danazol. Additionally, other data indicate that the danazol derivative increases left ventricular pressure in a dose-dependent manner; nevertheless, this phenomenon was significantly inhibited by flutamide. These data suggest that danazol derivative induces positive in...

Several studies indicate that some benzamide-derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the effects exerted by the benzamide derivatives on cardiac injury caused by ischemia/reperfusion (I/R). In this experimental study, a new benzamidederivative was synthetized with the objective of evaluating its activity on I/R in an I/R model of rat heart using the Langendorff technique. In addition, molecular mechanism involved in the effect induced by the benzamide derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of following compounds; nifedipine, indomethacin, propranolol and metoprolol. The results showed that the benzamide-derivative reduces infarct size compared with control. Other results showed that the benzamide derivative significantly increase the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the benzamidederivative increase left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); however, this phenomenon was significantly inhibited by propranolol and metoprolol at a dose of 1 nM (p=0.05). In conclusion, these data suggest that cardioprotective activity of the benzamide-derivative is by stimulating catecholamine production and consequently induce changes in the left ventricular pressure levels. This phenomenon results in decrease of myocardial necrosis after ischemia and reperfusion.

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