Local transfer of diazepam, but not of cocaine, from the nasal cavities tothe brain arterial blood in rats

Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial bloo d than in other arteries. The preferential distribution is based on a count er current transfer, which takes place between nasal vein blood and brain a rterial blood in the cavernous sinus - carotid artery complex. The present experiments attempt to document that drugs may also be transferred by this system. Groups of 10 large male rats were anaesthetised and intubated. Two catheters were inserted into the same carotid artery, one tip pointing towa rds the head, the other towards the heart. parallel blood samples were obta ined every 30 sec. for 10 min, after nasal administration of radioactively labelled diazepam or cocaine, and the plasma radioactivity measured. Contro l groups received the drugs intravenously. The uptake of diazepam was rapid , while cocaine uptake was slow. The average ratio between the radioactivit y of parallel samples (R: "Head" plasma/"Heart" plasma) in rats treated wit h nasal diazepam was 1.12+/-0.04, 181 (average+/-S.E.M, n) for the whole 10 min. period and 1.20+/-0.05, 96 for the second half of the sampling period . The increase of 12 and 20% is highly significant. The intravenous ratio f or diazepam and both R's for the cocaine groups were not significantly diff erent from 1.00. The present experiments show that nasal administration of diazepam induces a relatively higher concentration in the brain arterial bl ood than in parallel samples obtained from another artery. A preferential, first-pass distribution to the brain after nasal administration of diazepam may thus exist.