N,N'-diallylpentobarbital (DAPB) metabolites and their effects on pentobarbital-induced sleep and hepatic drug-metabolizing enzymes.
1. The biological half-life (t 1/2) of N,N'-diallylpentobarbital (DAPB) in brain after i.p. injection to mouse was 96 min (first phase) and 11 h (second phase). The t 1/2 values in plasma were 102 min and 9.4 h, respectively, after i.p. injection. After intracerebroventricular (i.c.v.) administration, the t 1/2 values in brain and plasma were 18 and 120 min, and 42 and 177 min, respectively. 2. Following i.p. administration of 2-14C-DAPB (80 mg/kg), 58% of the 14C was excreted in the urine in 72 h. Several urinary metabolites were identified by g.l.c.-mass spectrometry, DAPB was metabolized by three major pathways, i.e., omega-1 hydroxylation, epoxide-diol pathway and N-deallylation. 3. The effects of DAPB and its metabolites on pentobarbital (PB)-induced sleep were examined after i.p., i.v. and i.c.v. administration. Metabolite 1 [M-1; (omega-1)-hydroxy-DAPB], an active metabolite, exhibited the most potent prolonging effect. 4. M-1 and other metabolites, as well as unchanged DAPB, showed significant inhibitory effects on mouse hepatic drug-metabolizing enzymes.
Tateoka
Y
Y
Shinshin Chemical Industries Co. Ltd, Toyama, Japan.
Kimura
T
T
Watanabe
K
K
Yamamoto
I
I
Hume
A S
AS
Ho
I K
IK
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006207:Half-Life; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010424:Pentobarbital / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*
C047654:N,N-diallylpentobarbital; D006899:Mixed Function Oxygenases; D010424:Pentobarbital