assess their in vitro hypoglycemic effects. naproxen and cromolyn were successfully docked into the binding site of gsk-3β (both were fitted into its binding pocket). they exhibited electrostatic, hydrophobic, and hydrogen-bonding interactions with key amino acids within the binding pocket with binding interaction profiles similar to ar-a014418 (the known inhibitor). the negative charges of the carboxylic acid groups in both drugs interact electrostatically with the positively charged guanidine group of arg141. moreover, the hydrogen bonding interactions between carboxylic acid moieties of cromolyn and the ammonium groups of lys183 and lys60, in addition to π-stacking of the naphthalene ring system of naproxen with the phenolic ring of tyr134. antidiabetic effects of naproxen and cromolyn: in normal animal models, both drugs have showed dose-dependent reduction in blood glucose levels and rise in glycogen levels. in chronic type ii diabetic model, glucose levels were also reduced, and glycogen level and insulin levels were elevated in a dose-dependent manner with a reduction in plasma glucose. anti-obesity effects of naproxen and cromolyn: both drugs showed significant anti-obesity effects as they reduce body weight, resistin, and glucose levels in a dose-dependent manner. they were also found to elevate adiponectin, insulin, and c-peptide levels in a dose-dependent manner. famotidine famotidine is a specific, long-acting h2 antagonist that decreases gastric acid secretion. it is used in the treatment of peptic ulcer disease, gerd, and pathological hypersecretory conditions, like zollinger–ellison syndrome. (14,15) h2-receptor antagonists affect hormone metabolism, but their effect on glucose metabolism is not well established. (16) a study has revealed a glucose-lowering effect for famotidine. the study of famotidine binding to the enzyme has showed that famotidine can be docked within the binding pocket of gsk-3β making significant interactions with key points within the gsk-3β binding pocket. strong hydrogen bond interactions with the key amino acids pro-136 and val -135 and potential hydrophobic interaction with leu-188 were similar to those found in the ligand binding to the enzyme (ar-a014418). furthermore, famotidine showed high gsk-3β binding affinity and inhibitory activity due to interactions that stabilize the complex, namely hydrogen bonding of guanidine group in famotidine with the sulfahydryl moiety in cys-199; and electrostatic interactions between the same guanidine group with the carboxyl group in asp-200, the hydrogen bond between the terminal nh2 group, the oh of the tyr-143, and the hydrophobic interaction of the sulfur atom in the thioether with ile-62. in vitro studies showed that famotidine inhibits gsk-3β activity and increases liver glycogen reserves in a dose dependent manner. a fourfold increase in the liver glycogen level with the use of the highest dose of famotidine (4.4 mg/kg) was observed. also, famotidine has been shown to decrease serum glucose levels 30, and 60 minutes after oral glucose load in healthy individuals. curcumin curcumin, which is a constituent of turmeric spice, has flavoring and coloring properties. it has two symmetrical forms: enol (the most abundant forms) and ketone. curcumin has wide pharmacological activities: anti-inflammatory, anti-microbial, hypoglycemic, anti-oxidant, and wound healing effects. in animal models with alzheimer disease, it has anti-destructive effect of beta amyloid in the brain, and recently it shows anti-malarial activity. curcumin also has chemo preventative and anti-cancer effects., and it has been shown to attenuate oxidative stress and renal dysfunction in diabetic animals with chronic use. curcumin's mechanism of action is anti-inflammatory; it inhibits the nuclear transcriptional activator kappa b (nf-kb) that is activated whenever there is inflammatory response. nf-kb has two regulatory factors, ikb and gsk-3, which suggests curcumin directly binds and inhibits gsk-3b. an in vitro study confirmed gsk-3b inhibition by simulating molecular docking using a silico docking technique. the concentration at which 50% of gk-3b would be inhibited by curcumin is 66.3 nm. among its two forms, experimental and theoretical studies show that the enol form is the favored form due to its intra-molecular hydrogen bonding, and an nmr experiment show that enol form exist in a variety of solvents. olanzapine antipsychotic medications are increasingly used for schizophrenia, bipolar disorder, anxiety, and other psychiatric conditions atypical antipsychotics are more commonly used than first generation antipsychotics because they decrease the risk of extrapyramidal symptoms, such as tardive dyskinesia, and have better efficacy. olanzapine and atypical antipsychotics induce weight gain through increasing body fat. it also affects glucose metabolism, and several studies shows that it may worsen diabetes. a recent study shows that olanzapine inhibits gsk3 activity, suggesting olanzapine permits glycogen synthesis. a study of the effect of olanzapine on mouse blood glucose and glycogen levels showed a significant decrease in blood glucose level and elevation of glycogen level in mice, and the ic50% of olanzapine were 91.0 nm, which is considered a potent inhibitor. the study also illustrates that sub-chronic use of olanzapine results in potent inhibition of gsk3. pyrimidine derivatives pyrimidine analogues are antimetabolites that interfere with nucleic acid synthesis. some of them have been shown to fit the atp-binding pocket of gsk-3β to lower blood glucose levels and improve some neuronal diseases.