To study the different effects of clozapine and its metabolites on the intracellular Ca2+ concentration([Ca2+]i) in cells of isolated rat islets.

Under low or high glucose (3.3 mmol/L or 16.7 mmol/L), the cells of isolated rat islets was treated with 1 mmol/L clozapine, desmethyl-clozapine and clozapine N-oxide respectively, blank control group was also set, [Ca2+]i represented by fluorescence intensity was measured by laser scanning confocal microscope after cells were loaded with calcium sensitive fluorecent indicator Fluo-4/AM.

Under low glucose, as compared with the blank control group, inhibitive effect on [Ca2+]i in cells was found in clozapine group and desmethyl-clozapine group respectively (P<0.01); As compared with the base line(0min), [Ca2+]i in cells was decreased according to the prolonging of time in clozapine group and desmethyl-clozapine group (P<0.05; 0.01), and the inhibitive effect of clozapine was more intensive than desmethyl-clozapine (P<0.01). Under high glucose, as compared with the blank control group, inhibitive effect on [Ca2+]i in β-cells was also found in clozapine group and desmethyl-clozapine group respectively (P<0.01); As compared with the base line(0min), [Ca2+]i in cells was also decreased according to the prolonging of time in clozapine group and desmethyl-clozapine group (P<0.05; 0.01), but the inhibitive effect of desmethyl-clozapine was more intensive than clozapine (P<0.01). However, no effect was found in clozapine N-oxide group under low or high glucose (P>0.05).

Clozapine and desmethyl-clozapine both inhibit [Ca2+]i in cells of isolated rat islets so that they can inhibit insulin secretion.