Kinetics and brain uptake of COR3224, a new 2-amino-2-oxazoline, in rats.
COR3224, a new 2-amino2 oxazoline derivative, shows antidepressant activity in the rat. This study was designed to analyse the influence of dose ranging on the brain/plasma concentration ratio of this drug. Adult male rats (250-300gr, Sprague Dawley) were given orally 10, 40 and 160 mg/Kg radiolabelled 14C-COR3224 (30 microCi/kg) in aqueous solution and were sacrificed at 0.25; 0.5; 0.75; 1; 2; 4; 6; 8; 12; 16; 24; and 30 hours post dose (5 rats per time). Plasma and brain samples were analysed for total radioactivity (T.R.) by liquid scintillation and for COR3224 (U.P.) by reversed-phase liquid chromatography and electrochemical detection. A linear relationship was found between AUC and doses administered for both TR and UP plasmatic determinations. In opposite, cerebral AUC for TR and U.P were not proportional to dose, and the evolution of the brain/plasma concentration ratios showed higher values for the 10mg/kg dose than for the 40 and 160mg/kg doses.
Damaj
M I
MI
Lab. Pharmacologie et de Pharmacocinétique, Fac. de Pharmacie, Chatenay-Malabry, France.
Trouvin
J H
JH
Lambrey
B
B
Jacquot
C
C
D000818:Animals; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D010080:Oxazoles / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
D000928:Antidepressive Agents; D010080:Oxazoles; C056984:COR 32-24