PMID- 7736912
OWN - NLM
STAT- MEDLINE
DCOM- 19950605
LR  - 20141120
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 23
IP  - 2
DP  - 1995 Feb
TI  - Inactivation of constitutive hepatic cytochromes P450 by phencyclidine in the 
      rat.
PG  - 201-6
AB  - The purpose of this study was to determine whether phencyclidine (PCP) inhibits 
      constitutive hepatic cytochrome P450 (CYP) isozymes when administered to naive 
      adult male Sprague-Dawley rats. Animals were pretreated with PCP (25 mg/kg/day 
      for 2 days), killed 3 and 16 hr after the last dose, and liver microsomes 
      prepared. The washed microsomes were then assayed for benzphetamine, 
      methamphetamine (MA), and methylenedioxymethamphetamine (MDMA) N-demethylation 
      together with MDMA demethylenation and MA 4-hydroxylation activities. MDMA 
      demethylenation (low substrate concentration), MA 4-hydroxylation, and metoprolol 
      alpha-hydroxylation reactions, which are catalyzed by CYP2D isozymes, were 
      reduced > 74% 3 hr after the last PCP dose and were only partially restored 13 hr 
      later. Benzphetamine and (-)-MDMA N-demethylation activities were restored to 
      control values 16 hr after the last dose. These results indicate that PCP 
      suppresses constitutive isozymes, including CYP2C11 and members of the CYP2D 
      subfamily. The suppression of cytochromes P450 activity by PCP in vivo is 
      consistent with its in vitro actions found in this and other studies, and 
      demonstrates that alteration of CYP activity is another pharmacological effect of 
      this compound.
FAU - Hiratsuka, A
AU  - Hiratsuka A
AD  - Department of Molecular and Medical Pharmacology, UCLA School of Medicine 
      90024-1735, USA.
FAU - Chu, T Y
AU  - Chu TY
FAU - Distefano, E W
AU  - Distefano EW
FAU - Lin, L Y
AU  - Lin LY
FAU - Schmitz, D A
AU  - Schmitz DA
FAU - Cho, A K
AU  - Cho AK
LA  - eng
GR  - DA02411/DA/NIDA NIH HHS/United States
GR  - DA04206/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Amphetamines)
RN  - 0 (Cyanides)
RN  - 0 (Cytochrome P-450 Enzyme Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - J1DOI7UV76 (Phencyclidine)
SB  - IM
MH  - Amphetamines/pharmacokinetics
MH  - Animals
MH  - Biotransformation
MH  - Cyanides/pharmacology
MH  - *Cytochrome P-450 Enzyme Inhibitors
MH  - Cytochrome P-450 Enzyme System/drug effects/*metabolism
MH  - Drug Interactions
MH  - Enzyme Activation
MH  - Isoenzymes/*antagonists & inhibitors/drug effects/*metabolism
MH  - Liver/*drug effects/*enzymology
MH  - Male
MH  - Microsomes, Liver/drug effects/enzymology
MH  - Phencyclidine/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
PST - ppublish
SO  - Drug Metab Dispos. 1995 Feb;23(2):201-6.