H. Yu et al., ORAL CAVITY ABSORPTION OF (R)-8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN AND (S)-8-ACETYL-2-(DI-N-PROPYLAMINO)TETRALIN IN THE RAT, Journal of Pharmacy and Pharmacology, 48(1), 1996, pp. 41-45
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.