Abstract
The brain uptake index (BUI) of L-tryptophan and diazepam into the right and left hemispheres and the cerebellum has been measured after a bolus injection into the carotid artery of the anaesthetised rat. The effect of a range of albumin concentrations (38 microM to 1.4 mM; 0.25-9 g/100 ml) on the viscosity and osmotic pressure of the bolus was studied as a preliminary to the brain uptake experiments. Dextran (Mr 60,000-90,000) was included in the injection to ensure constant viscosity and osmotic pressure. An increase in albumin concentration up to 2 g/100 ml substantially reduced the BUI of L-tryptophan, but a further increase in albumin concentration up to 9 g/100 ml resulted in only a slow fall in the BUI of L-tryptophan which was not proportional to the larger fall in the concentration of unbound L-tryptophan. Furthermore, the use of norharmane as an inhibitor of L-tryptophan binding did not reveal a simple relationship between its unbound concentration and BUI. A decrease in the unbound concentration of diazepam also reduced its BUI, but again there was no straightforward relationship between this and unbound diazepam concentration. The differences observed in the BUI of inulin from solutions of either dextran or albumin indicate not only that each macromolecule may exert particular effects on the BUI, perhaps by an influence on cerebral blood flow, but also show how difficult it is to devise solutions for injection which differ in respect of only one variable, that of the unbound ligand concentration.
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