Active substances: Amoxicillin
Finally, our study was performed in male Wistar rats and Martins et al. The measurements of the plasma Olanzapine concentrations that we performed in samples taken immediately at the end of the infusion showed a small, but detectable, amount of Olanzapine 1.
Unfortunately, in the study of Martins et al. However, since even with our low dose, Olanzapine passed from the ventricle to the plasma, higher doses of Olanzapine most likely will increase the level of Olanzapine in plasma even further and thus make it very difficult to distinguish between a central and a peripheral effect.
In the light of the current data, it is plausible that a combination of the 3 rd ventricle injection site and a 10-fold higher dose would possibly result in a leakage of Olanzapine to the peripheral circulation.
The clamp experiments Experiments 2 and 3 showed a clear hepatic and extra-hepatic insulin resistance that likely contributes to the increased glycemia following Olanzapine infusion. Since in Experiment 1 hepatic glucose production was not significantly increased this would indicate a non-hepatic reduction in glucose uptake as the primary mechanism of Olanzapine to induce hyperglycemia.
Corticosterone levels of Olanzapine-treated animals were elevated, but it is unlikely that this hormone causes the observed hyperglycemia as the increase was not sufficient to induce changes in hepatic glucose production.
On the other hand, glucocorticoids are also involved in the regulation of insulin secretion,, and, although in our study plasma insulin levels remained unchanged during Olanzapine treatment, the lack of an increased insulin secretion could facilitate the hyperglycemic effect of Olanzapine.
Recently, it has been shown that selective glucocorticoid receptor type 2 antagonists are able to prevent the weight gain in rats induced by chronic Olanzapine treatment.
Belanoff et al. However, the mechanisms underlying glucocorticoid antagonist mediated inhibition of weight gain have not been fully elucidated yet.
Nevertheless, these data indicate the glucocorticoid receptor as an interesting target for preventing the metabolic side-effects of Olanzapine. MacKay and Daniel E.
Anthony J. Carrasquillo, Gregory L.
Bruland, Allison A. Amanda L.
Mifflin, Christopher T. Konek, and, Franz M. The Journal of Physical Chemistry B, 110 45, 22577- Wagner, Jie Zhuang, Xijuan Chen.