Preclinical pharmacokinetic and toxicological evaluation of MIF-1 peptidomimetic, PAOPA: Examining the pharmacology of a selective dopamine D2 receptor allosteric modulator for the treatment of schizophrenia

Article ID	Journal	Published Year	Pages	File Type
8348844	Peptides	2013	8 Pages	PDF

Abstract

âº Study investigated allosteric peptide, PAOPA, specific for the dopamine D2 receptor. âº Study of PAOPA distribution showed it to effectively cross the blood-brain barrier. âº Pharmacokinetic profile of PAOPA was examined in rats across various time points. âº Toxic effects were examined through necropsy, histopathology, and blood analyses. âº Study showed robust drug safety, and thus platforms its progress to clinical trials.

Keywords

AUMC 5-hydroxytryptamine HOMA-IR i.p.p.o.6-Hydroxydopamine tmax i.v.HDL 5-HT2 PLG AUCinf AUClast TSQ MIF-1 6-OHDA PAOPA Cmax VCMs LLQ AUC H&E high-density lipoprotein HPLC–MS t1/2 VSs Allosteric Homeostatic model assessment Schizophrenia total body clearance intraperitoneal injection Volume of distribution volume of distribution at steady state maximum plasma concentration vacuous chewing movements Intravenous Antipsychotic CNS time to maximum plasma concentration Toxicology central nervous system High performance liquid chromatography–mass spectrometry Pharmacokinetics Low-density lipoprotein LDL limit of quantitation Allosteric modulator area under curve Half-life Hematoxylin and Eosin HILIC hydrophilic interaction chromatography D2 receptor