Brain distribution discovery

There are limited peptidic inhibitors of the 7.4(52 subtype, and given its wide distribution in the brain, the discovery of novel inhibitors for this subtype is of significant interest.158 The unusual N-terminal tail of GID was shown to be important for activity at the 7.4(52 subtype and prompted NMR studies of structure-activity relationships of GID.157,15 The NMR structure of GID157 shows the characteristic fold of the a-conotoxins but the N-terminal tail is disordered in... 

Abraham, M.H., Chadha, H.S. and Mitchell, R.C. (1995). Hydrogen Bonding. Part 36. Determination of Blood Brain Distribution Using Octanol-Water Partition Coefficients. Drug Design Discovery, 13,123-131. 

Neurexins Discovery, Domain Structure, and Brain Distribution... 

Membrane permeability is one of the most important determinants of pharmacokinetics, not only for oral absorption, but also for renal re-absorption, biliary excretion, skin permeation, distribution to a specific organ and so on. In addition, modification of membrane permeability by formulation is rarely successful. Therefore, membrane permeability should be optimized during the structure optimization process in drug discovery. In this chapter, we give an overview of the physiology and chemistry of the membranes, in vitro permeability models and in silica predictions. This chapter focuses on progress in recent years in intestinal and blood-brain barrier (BBB) membrane permeation. There are a number of useful reviews summarizing earlier work [1-5]. 

The discovery of monocarboxylate transporters (MCTs), their characterization, and the study of their distribution has been a major landmark, and it provides interesting clues about their possible roles in regulating monocarboxylate fluxes not only between the blood and the brain but also between the different intraparenchymal cell types. Monocarboxylate transporters may represent an important site for both entry and exit of numerous substances, including several pharmaceuticals, in the brain [79]. 

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