Penetration of some O-and/or N-methylated norepinephrine derivatives through the rat blood brain barrier.

Methods for the determination of a number of O and/or N-methylated derivatives of norepinephrine were developed. The IP injection of these compounds into rats shows quick absorption and short half-lives in plasma, liver and brain. Most compounds do not cross the Blood-Brain-Barrier (BBB) due to low lipid solubility. However, lipid solubility is not a sole determinant. Compounds which have at least one of the 2 phenolic hydroxyl groups methylated and possess a tertiary amino group do cross the BBB readily.