PMID- 712637
OWN - NLM
STAT- MEDLINE
DCOM- 19790126
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 207
IP  - 2
DP  - 1978 Nov
TI  - Metabolism of amphetamine after acute and chronic administration to the rat.
PG  - 544-54
AB  - The distribution of amphetamine (AMPH) and its hydroxylated metabolites 
      p-hydroxyamphetamine (POHA), p-hydroxynorephedrine (POHNOR) and 
      p-hydroxyamphetamine glucuronide (POHAG) in various tissues was studied after 
      acute and chronic administration of AMPH to rats. After intraperitoneal 
      administration of a single dose of [3H]AMPH, tissue [3H]AMPH levels increased 
      rapidly to a maximum within 15 to 20 min of administration and then declined 
      biphasically [(t1/2 = 0.5--0.9 hr for the distribution phase (alpha) and 5--9 hr 
      for the elimination phase (beta)]. Tissue [3H]POHA levels and liver [3H] POHAG 
      levels also increased rapidly and then declined exponentially (t1/2 = 4--10 hr 
      for POHA), while tissue [3H]POHNOR increased gradually and declined with a 
      half-life of 18 to 24 hr. The distribution of [3H]AMPH and its 3H-metabolites 
      after a single dose of [3H] AMPH changed significantly after chronic 
      administration of amphetamine. [3H]AMPH content in tissues of chronically treated 
      rats was significantly greater 30 min after [3H]AMPH administration than that 
      observed in tissues of animals not previously treated with AMPH. The 
      disappearance of [3H]POHA from liver and [3H]POHNOR from heart was accelerated 
      and the disappearance of [3H] POHAG from liver was slowed in chronically treated 
      animals relative to controls, while the half-life of [3H]AMPH was unchanged in 
      these animals. Tissue content of both AMPH and POHNOR 12 hr after the last of six 
      doses of AMPH was significantly greater than that observed after a single dose, 
      suggesting that significant accumulation of both compounds occurs during chronic 
      AMPH administration. These studies suggest that the changes in the distribution 
      of AMPH and its active metabolites which occur during chronic AMPH administration 
      might be involved in the altered behavioral response to AMPH observed during such 
      chronic administration.
FAU - Kuhn, C M
AU  - Kuhn CM
FAU - Schanberg, S M
AU  - Schanberg SM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - CK833KGX7E (Amphetamine)
SB  - IM
MH  - Amphetamine/administration & dosage/*metabolism
MH  - Animals
MH  - Half-Life
MH  - Male
MH  - Rats
MH  - Time Factors
MH  - Tissue Distribution
EDAT- 1978/11/01 00:00
MHDA- 1978/11/01 00:01
CRDT- 1978/11/01 00:00
PHST- 1978/11/01 00:00 [pubmed]
PHST- 1978/11/01 00:01 [medline]
PHST- 1978/11/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1978 Nov;207(2):544-54.