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 decreasing body temperature after administration of the compound subcutaneously into the gastric ventricle or into the oral cavity in the rat. The dose range eliciting a clear-cut HT1A syndrome and hypothermia after oral cavity administration was 1/10-1/30 that of the gastric ventricle 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. Determination of the concentrations of (R)-8-OH-DPAT in plasma and brain tissue confirmed a higher bioavailability after oral cavity than after gastric ventricle administration; plasma and brain tissue concentrations of the drug were found to be approximately 3 times those after 10 mumol/kg-1 orally than after 100 mumol/kg-1 gastroventrically at 15-60 min after administration of (R)-8-OH-DPAT. These findings suggest 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 bioavailability.
Yu
H
H
Department of Psychiatry (Ulleråker), Uppsala University, Sweden.
Liu
Y
Y
Hacksell
U
U
Lewander
T
T
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000042:Absorption; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
D017366:Serotonin Receptor Agonists; D013764:Tetrahydronaphthalenes; C079940:8-acetyl-2-(dipropylamino)tetralin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin