Date of Award
The treatment of psychological diseases like schizophrenia has depended on the use of antipsychotic drugs many of which were created as far back as the 1970’s. These drugs typically act on the D2 dopamine receptor (D2R) to antagonize its signaling and alter the signaling of the mesolimbic and mesocortical dopaminergic pathways in the brain. Several studies have indicated that it may be more important to identify the specific receptor-protein interactions which could prove to be more beneficial drug targets for the treatment of schizophrenia (Magalhaes, Dunn, & Ferguson, 2012). In this study we identified that the fourth transmembrane motif in D2R is responsible for the receptor-protein interaction that was previously shown to decrease the detergent solubility of cellular Gβ5. Furthermore, we showed that the biophysical effects of this receptor-protein interaction could be significantly altered by treatment with clozapine but not haloperidol. Clozapine is a first generation antipsychotic that has been shown to have a unique efficacy for the treatment of schizophrenia compared to all other antipsychotics (Attard & Taylor, 2012). This finding identifies both a unique property of clozapine binding to the receptor and a significant alteration of receptor-protein interactions by a drug that previously was only thought to simply antagonize DA signaling at D2R.
Irving, Craig Michael, "Receptor-Protein Interactions Mediated by the Fourth Transmembrane of D2R can be Altered by Treatment with Antipsychotics" (2017). Open Access Master's Theses. Paper 1060.
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