ORAL CAVITY ABSORPTION OF (R)-8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN AND (S)-8-ACETYL-2-(DI-N-PROPYLAMINO)TETRALIN IN THE RAT

The present communication reports on the efficacy of (R)-8-OH-DPAT ((R )-8-hydroxy-2-(di-n-propylamino)tetralin) and (S)-LY-41 ((S)-8-acetyl- 2-(di-n-propylamino)tetralin) in displaying the 5-HT1A syndrome and de creasing body temperature after administration of the compound subcuta neously into the gastric ventricle or into the oral cavity in the rat. The dose range eliciting a clear-cut 5-HT1A syndrome and hypothermia after oral cavity administration was 1/10-1/30 that of the gastric ven tricle dose range, but 10-30 times higher than the dose range used for subcutaneous administration of both (R)-8-OH-DPAT and (S)-LY-41. Dete rmination of the concentrations of (R)-8-OH-DPAT in plasma and brain t issue confirmed a higher bioavailability after oral cavity than after gastric ventricle administration; plasma and brain tissue concentratio ns of the drug were found to be approximately 3 times those after 10 m u mol kg(-1) orally than after 100 mu mol kg(-1) gastroventrically at 15-60 min after administration of (R)-8-OH-DPAT. These findings sugges t that the oral cavity may be an important site for drug delivery of 8 -OH-DPAT, LY-41 and other compounds with a low gastrointestinal bioava ilability.