Blood-brain barrier, permeability

Liu X, Tu M, Kelly RS, Chen C and Smith BJ. Development of a computational approach to predict blood-brain barrier permeability. Drug Metab Dispos 2004 32 132-9. 

Suomalainen, P., Johans, G., Soderlund, T., Kinnunen, P. K. Surface activity profiling of drugs applied to the prediction of blood-brain barrier permeability. J. Med. Chem. 2004, 47, 1783-1788. 

Dudley, A., Beliveau, R. P-glycoprotein deficient mouse in situ blood-brain barrier permeability and its predicfion using an in comho PAM PA model, (under review)... 

Oa radicals in arachidonate-induced increased blood-brain barrier permeability to proteins. Am. J. Physiol. 251, H693-699. 

Poduslo JF, Curran GL, Kumar A, Frangione B, Soto C. Beta-sheet breaker peptide inhibitor of Alzheimer s amyloidogenesis with increased blood-brain barrier permeability and resistance to proteolytic degradation in plasma. J Neurobiol 1999 39 371-382. 

Tmovec, T., Z. Kallay, and S. Bezek. 1990. Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances. Inter. Jour. Radiation Oncol. Biol. Physics 19 1581-1587. 

The complete role of N,N-dialkyl substitution is not fully understood, although it serves to enhance blood-brain barrier permeability and to hinder metabolic inactivation. 

N,N-Dialkyltryptamines bearing an alkyl substituent on the aromatic nucleus have not been evaluated in man, and only data from animal studies are available. Taborsky et al. (228) found 1-methylation to have variable effects on behavioral activity. This might reflect blood-brain barrier permeability. Methylation at the N1 position of DMT (37), to give 1, N,N-trimethyltryptamine (1-TMT), had... 

Neurological effects occurred in animals exposed to endrin. Behavioral effects (Gray et al. 1981), hyperexcitability, tremors, and convulsions (Deichmann et al. 1970 NCI 1978 Treon et al. 1955) were reported. Irregular EEG recordings were observed in rats (Speck and Maaske 1958). There is some evidence to show that occurrence of convulsions is related to blood-brain barrier permeability changes (Speck and Maaske 1958). 

The rather time- and cost-expensive preparation of primary brain microvessel endothelial cells, as well as the limited number of experiments which can be performed with intact brain capillaries, has led to an attempt to predict the blood-brain barrier permeability of new chemical entities in silico. Artificial neural networks have been developed to predict the ratios of the steady-state concentrations of drugs in the brain to those of the blood from their structural parameters [117, 118]. A summary of the current efforts is given in Chap. 25. Quantitative structure-property relationship models based on in vivo blood-brain permeation data and systematic variable selection methods led to success rates of prediction of over 80% for barrier permeant and nonper-meant compounds, thus offering a tool for virtual screening of substances of interest [119]. 

Garg P, Verma J (2006) In silico prediction of blood-brain barrier permeability An artificial neural network model. J Chem Inf Model 46 289-297... 

In Silico Modeling for Blood-Brain Barrier Permeability Predictions... 

Murakami H, Takanaga H, Matsuo H, Ohtani H, Sawada Y (2000) Comparison of blood-brain barrier permeability in mice and rats using in situ brain perfusion technique. Am J Physiol 279 H1022-H 1028. 

Figure 2.5. Setup for in vitro measurement of blood-brain barrier permeability with a co-culture of bovine brain microvascular endothelial cells (BBMEC) and an astro ioma cell line, C6. The BBMEC are grown on top of a filter insert. The C6 cells are either grown on the opposite side of the filter or on the bottom of the wells. Transport across the BBMEC monolayer is measured by adding the test substance to the upper chamber and sampling from the lower chamber. The tightness of the monolayer is also characterized by the transendothelial electrical resistance (TEER). Courtesy of T. Abbruscato.

Plasma clearance (Cl), blood-brain barrier permeability surface area product (PS) and accumulation as % injected dose detected in brain tissue (%ID tissue) at 1 h after administration. Results show free [ H]-daunomycin (Daunomycin), [ H]-daunomycin encapsulated in conventional liposomes (Liposomes), sterically stabilized liposomes (PEG-liposomes), immunoliposomes (29 0X26, where 29 designates the number of 0X26 mAb conjugated per liposome) and control immunoliposomes where the 0X26 mAb was replaced by a non-specific isotype control antibody (IgG2a). Values are means SEM of n = 3 experiments. 

Fig. 1.2 4-Hydroxyquinolines with improved oral absorption and blood-brain barrier permeability [15].

Kortagere, S., Chekmarev, D., Welsh, W.J., Ekins, S. New predictive models for blood-brain barrier permeability of drug-like molecules. Pharm. Res. 2008, 25, 1836—45. 

Blood-Brain Barrier Permeability Thermodynamic Solubility in Water... 

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