Transient blood-brain barrier passage of polar compounds at low pH.

The brain uptake index (BUI) of polar 14C-labeled test compounds with molecular weights (MWs) of 79-70,000 was examined using the single-pass carotid injection technique in pentobarbital-anesthetized rats. Compounds were injected in 40 mM malonate, pH 2.5, and 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, pH 7.

Blood-brain barrier: penetration of morphine, codeine, heroin, and methadone after carotid injection.

Labeled morphine, codeine, heroin, or methadone was injected as a bolus into the common carotid artery of the rat, and the rat was decapitated 15 seconds later. The brain uptake of the drug was calculated by measurement of the brain content of the drug as a percentage of a labeled, highly diffusible reference substance simultaneously injected. The uptake of morphine was below measurability; the uptake of codeine was 24 percent; heroin, 68 percent; and methadone, 42 percent.