Absorption of the new anxiolytic compound deramciclane in rats, dogs and rabbits

• Published in: Arzneimittel-Forschung Vol. 48; no. 5; p. 455
• Main Authors: Lengyel, J, Bolehovszky, A, Klebovich, I, Aberman, M, Magyar, K
• Format: Journal Article
• Language: English
• Published: Germany 01-05-1998
• Subjects: Animals; Anti-Anxiety Agents - adverse effects; Anti-Anxiety Agents - blood; Anti-Anxiety Agents - pharmacokinetics; Area Under Curve; Bornanes - adverse effects; Bornanes - blood; Bornanes - pharmacokinetics; Chromatography, Thin Layer; Dogs; Female; Intestinal Absorption; Male; Mass Spectrometry; Rabbits; Rats; Rats, Wistar; Species Specificity
• ISSN: 0004-4172

The absorption of deramciclane fumarate ((1R,2S,4R)-(-)-N,N-dimethyl-2-[(1,7,7-trimethyl-2-phenylbicyclo [2,2,1] hept-2-yl) oxy] ethane amine-2-(E)-butenedioate (1:1), CAS 120444-78-8, EGIS-3886), a new anxiolytic compound, was studied in rats, dogs and rabbits by using 3H-camphor- or 14C-phenyl-labelled radioisomers of the substance. The compound was readily absorbed from the intestinal tract after oral administration. The absorption of 14C-deramciclane was also studied from the isolated intestinal loops of rats (duodenal, jejunal, ileal loops) and dogs (duodenal loop). The absorption was faster in rats and rabbits than in dogs (tmax = 1 h or 6 h, respectively). The radioactivity was not absorbed from the isolated stomach of any species studied for 2 h. Meanwhile, the substance was not decomposed by the gastric juice, as it has been proved by TLC and MS analyses. Deramciclane is preferentially excreted via the bile. The intensity of its bile excretion is higher in rats than in dogs. Higher plasma levels of labelled deramciclane were found in female than in male rats.