Whole-body autoradiography and quantitative organ-level distribution study of deramciclane in rats.
The distribution of 3H-labelled deramciclane (EGIS-3886), a new 5-HT2 antagonist with anxiolytic activity, has been investigated by whole-body autoradiography and quantitative organ-level determination after intravenous and oral administration to male and female rats at a dose of 3 mg kg(-1). Pregnant dams were also studied, but by autoradiography only. In the autoradiographic study 32 organs were investigated, while in the quantitative organ-level study the radioactivity in 15 organs were determined. There are no sex differences in the distribution of deramciclane, absorption is rapid, elimination is comparatively fast, no specific organ is targeted, and the accumulation of the compound is very unlikely. Penetration of the blood-brain barrier was complete and extremely fast, a very important feature of a potential anxiolytic drug. There is no penetration of the foetus in pregnant dams. The study demonstrated that deramciclane has advantageous pharmacokinetic properties in rats.
Hazai
I
I
Institute for Drug Research, Department of Pharmacokinetics, Budapest, Hungary.
Pátfalusi
M
M
Klebovich
I
I
Urmös
I
I
D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography / Q000379:methods*; D001892:Camphanes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005629:Frozen Sections; D007275:Injections, Intravenous; D008297:Male; D011247:Pregnancy; D051381:Rats; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium
D001892:Camphanes; D012702:Serotonin Antagonists; D014316:Tritium; C060555:deramciclane