The blood-brain barrier penetration of tetrahydropapaveroline (THP) was studied in male rats of the Sprague-Dawley strain. THP was not found in brains of untreated animals. However, THP was observed in the brains of animals that received THP-HBr by intraperitoneal (IP) injection 30 minutes before decapitation. Animals that received IP injections of 0.10, 1.0, 5.0, or 10 mg THP-HBr/kg exhibited brain levels of 3.1, 25, 95 or 126 pmoles THP per gram brain, respectively. Another group of rats received THP-HBr (5.0 mg/kg) IP 30 minutes before decapitation. The brain of each animal was dissected into nine regions and each region assayed for THP. All brain regions assayed had measurable levels of THP. The highest concentration of THP (132 pmoles/g) was observed in the olfactory lobes-frontal cortex while the lowest concentration of THP (27.3 pmol/g) was in the striatum. These results demonstrate that THP penetrates the blood-brain barrier in rats. They also suggest that if THP is formed in the periphery, it may penetrate the blood-brain barrier, and be localized in discrete brain regions.
