Brain pharmacokinetics of centrally acting drugs, a quantitative autoradiographic study.
The concentration kinetics of 14C labeled diazepam, chlorpromazine and iodoantipyrine were studied in several regions of rat brain shortly after intravenous (i.v.) administration by a quantitative autoradiographic method. A highly significant linear relationship was found between regional diazepam resp. chlorpromazine concentration, and regional cerebral blood flow (rCBF) 1 min after injection. Moreover, a linear relationship was found between rCBF and, on the other hand, firstly diazepam concentration decrease between 1 and 2 min, secondly increase in chlorpromazine concentration between 1 and 5 min, and finally decrease of chlorpromazine concentration between 5 and 30 min. The regional kinetics of diazepam were compared with those of iodoantipyrine, a tracer assumed to be freely diffusible through the blood-brain barrier.
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D002746:Chlorpromazine / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism*; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003975:Diazepam; D000983:Antipyrine; D002746:Chlorpromazine; C008135:iodoantipyrine