Abstract
Olanzapine was investigated as an inhibitor of glycogen synthase kinase-3β (GSK-3β) in an attempt to evaluate its effect on blood glucose level. The investigation included simulated docking experiments to fit olanzapine within the binding pocket of GSK-3β followed by in vitro enzyme inhibition assay as well as in vivo subchronic animal treatment. Olanzapine was found to readily fit within the binding pocket of GSK-3β in a low energy orientation characterized with optimal attractive interactions bridging the tricyclic thienobenzodiazepine nitrogen and sulfur atoms of olanzapine and the residue of VAL-135 of GSK-3β. In vivo experiments showed a significant decrease in fasting blood glucose level in Balb/c mice at 1.0, 2.0 and 3.0 mg/kg dose levels ( P < 0.05) and 6 fold increase in liver glycogen level at the 3 mg/kg dose level ( P < 0.001). Moreover; olanzapine was found to potently inhibit recombinant GSK-3β in vitro (IC 50 value = 91.0 nM). Our findings strongly suggest that olanzapine has significant GSK-3β inhibition activity that could justify some of its pharmacological effects and glucose metabolic disturbances.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
