Studies of the side chain cleavage of deramciclane in rats with radiolabelled compounds.
The pharmacokinetics of deramciclane and especially the fate of its side chain were studied in rats after oral treatment, using (3)H- and (14)C-labelled (ring- or side chain labelled) deramciclane and (14)C-dimethylamino-ethanol ((14)C-DMAE) radioisomers. The labelled compounds were admixed and the total radioactivities of both labels were simultaneously determined. The data obtained from the analysis of the plasma concentration-time curves revealed that an intensive cleavage (30-40%) of the side chain occurred at the ether bond. The core of deramciclane, carrying the ring label, was almost completely eliminated during 24 h, while the elimination of the side chain was very slow (t(1/2)(beta): 99 h). The side chain residue most probably represents dimethylamino-ethanol, but the presence of dimethylglycine (DMG) cannot be excluded. The AUC(0-infinity) and the MRT values of DMAE were found to be much higher than those of the parent compound. In addition to the plasma levels, the time related changes of the tissue concentrations of the radioisomers of deramciclane were analysed both in the brain and the hypophysis. The concentration-time curves have shown similar characteristics to those of the plasma, but higher concentrations were reached in both organs (the highest in the hypophysis). It is postulated that the low rate of formation and elimination of the metabolite(s) (DMAE or DMG) indicates that, due to their endogenous nature, they can be incorporated into choline/acetylcholine or protein synthesis.
Magyar
Kálmán
K
Central Isotope Laboratory, Semmelweis University, PO Box 370, H-1445 Budapest, Hungary. magykal@net.sote.hu
Lengyel
József
J
Bolehovszky
Andrea
A
Grézal
Gyula
G
Klebovich
Imre
I
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D001892:Camphanes / Q000097:blood / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D014151:Anti-Anxiety Agents; D001892:Camphanes; D002250:Carbon Radioisotopes; D014316:Tritium; C060555:deramciclane