Pharmacological Studies on the Possible Interaction between some psychotropics & certain Antidiabetics

Sulfonylureas have been used for more than twenty years to treat diabetic patient The role of the pancreas in the hypoglycemic action of sulfonylureas .has been established by the pioneer work. of” Loubatiers (1957), and was confirmed by the demonstration that these drugs stimulate insulin release in man (Yallow etal., 1960) and animals (Seltzer; H.S., 1962) by a dire ct effect on” B ce lls .d ernonstra ted in vitro (Bouma nand Goorenstroorn, 1961). This insulinotropic action of acute administration of sulfonyluFeas has since been extensively studied:It is generally suggested that sulfony lureas, : depolarize beta cells ’by ’reducing their K+ permeability., This I’depolarization leads to opening of voltage-dependent , calcium channels and the resulting . Ca 2+ influx triggers insulin release (Henquin, 1980)A possible need for the use .of neuroleptics such as phenothiazines in diabetic patients has been pointed out by Vanden Gerg and Sussman ( 1969:).On the other hand, hyperglycemia following -t he administration of phenothiazines had been also reported (Ammon et al~, 1973). ’This effect might present a potential hazard if such drugs are given to patient who are concomitantly receiving antidiabetic agents. Moreover, Abdel..; Ghany et al., (1985) found significant interaction between phenothiazines and some antidiabetic agents in vivo.Therefore, it is of interest to investigate in vitro the mechanisms by which the antipsychotic drugs fluphenzine (FPZ) and Triflouoperazine (TFP) inhibit the tolbulamide mediated insulin secretion. The effect of FPZ and TFP on the tolbutamide stimulated insulin release, of 86Rb efflux (as a marker for potassium efflux) and Ca2+ uptake were investigated.The calcium regulatory protein calmodulin reversibly binds calcium, the Ca2+ -calmodulin complex has been shown to regulate a wide variety of. ’enzymes ,involved in the enzyme secretory process.