During the course of drug discovery translational steps are made. The translation from in vitro to in vivo experiments is not as predictive as one would desire, resulting in selection of... Show moreDuring the course of drug discovery translational steps are made. The translation from in vitro to in vivo experiments is not as predictive as one would desire, resulting in selection of inefficacious compounds but also in overlooking of promising drug candidates. This is not different for the mGlu2 receptor for which no drugs are available on the market so far despite enormous drug discovery efforts. Therefore, there is a need to improve the molecular understanding of key in vitro parameters that drive in vivo efficacy. Hence, this thesis focuses on the concepts of target binding kinetics and functional efficacy of both allosteric and orthosteric ligands of the mGlu2 receptor. Show less
Electroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to produce generalized seizure for the treatment of selected psychiatric disorders, mostly... Show moreElectroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to produce generalized seizure for the treatment of selected psychiatric disorders, mostly treatment resistant depression, acute mania, and schizophrenic syndromes. Safety of ECT increases the efficacy of therapy and provides fulfillment of a series of required treatments resulting in longer treatment effect of ECT. During the last few decades, researchers have been attempting to improve the effectiveness of ECT, to learn how and why it works, and to understand its risks and adverse side effects. As a result, the safety and efficacy of ECT has been improved and its indications have been relatively defined to increase the efficiency of outcome of therapy. While there has been considerable improvement in safety features, further investigation have been done to promote both the safety and efficacy of the treatment. Such efforts could increase our knowledge on the biological mechanisms involved in effectiveness of ECT that might result in discovery of new treatments. In this dissertation, we investigate how preprocedural medications could improve the safety and efficacy of ECT and further investigated the potential role of pharmacogenetics in the efficacy of ECT and procedural side effects such as cognitive disorders. Show less
