TY - JOUR T1 - The Grasshopper: A Novel Model for Assessing Vertebrate Brain Uptake JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 211 LP - 218 DO - 10.1124/jpet.113.205476 VL - 346 IS - 2 AU - Olga Andersson AU - Steen Honoré Hansen AU - Karin Hellman AU - Line Rørbæk Olsen AU - Gunnar Andersson AU - Lassina Badolo AU - Niels Svenstrup AU - Peter Aadal Nielsen Y1 - 2013/08/01 UR - http://jpet.aspetjournals.org/content/346/2/211.abstract N2 - The aim of the present study was to develop a blood-brain barrier (BBB) permeability model that is applicable in the drug discovery phase. The BBB ensures proper neural function, but it restricts many drugs from entering the brain, and this complicates the development of new drugs against central nervous system diseases. Many in vitro models have been developed to predict BBB permeability, but the permeability characteristics of the human BBB are notoriously complex and hard to predict. Consequently, one single suitable BBB permeability screening model, which is generally applicable in the early drug discovery phase, does not yet exist. A new refined ex vivo insect-based BBB screening model that uses an intact, viable whole brain under controlled in vitro-like exposure conditions is presented. This model uses intact brains from desert locusts, which are placed in a well containing the compound solubilized in an insect buffer. After a limited time, the brain is removed and the compound concentration in the brain is measured by conventional liquid chromatography-mass spectrometry. The data presented here include 25 known drugs, and the data show that the ex vivo insect model can be used to measure the brain uptake over the hemolymph-brain barrier of drugs and that the brain uptake shows linear correlation with in situ perfusion data obtained in vertebrates. Moreover, this study shows that the insect ex vivo model is able to identify P-glycoprotein (Pgp) substrates, and the model allows differentiation between low-permeability compounds and compounds that are Pgp substrates. ER -