PMID- 1374469
OWN - NLM
STAT- MEDLINE
DCOM- 19920605
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 261
IP  - 2
DP  - 1992 May
TI  - Effect of flunarizine and nimodipine on the decrease in tryptophan hydroxylase 
      activity induced by methamphetamine and 3,4-methylenedioxymethamphetamine.
PG  - 586-91
AB  - The effect of calcium channel blockers on the decrease in central tryptophan 
      hydroxylase (TPH) activity and serotonin (5-HT) concentration induced by repeated 
      large doses of methamphetamine (METH) or 3,4-methylenedioxymethamphetamine (MDMA) 
      was evaluated. Rats received four or five injections of METH (10 or 15 mg/kg) or 
      MDMA (10 mg/kg) at 6-h intervals, and were sacrificed 18 to 20 h or 1 week after 
      the last administration. Flunarizine (30 mg/kg) prevented the decline in cortical 
      and neostriatal TPH activity induced by MDMA, but failed to alter the effect of 
      METH. The effect of flunarizine on the METH- and MDMA-induced changes in cortical 
      5-HT and 5-hydroxyindoleacetic acid concentrations paralleled the changes in 
      enzyme activity. Nimodipine, diltiazem or TA-3090 failed to prevent the MDMA- and 
      the METH-induced decline in TPH activity or in 5-HT and 5-hydroxyindoleacetic 
      acid content. Because haloperidol failed to mimic the protective action of 
      flunarizine, it is unlikely that flunarizine exerts its action by blocking the 
      dopamine D-2 receptors. This study suggests that calcium influx may participate 
      in the MDMA-induced decline in central TPH activity, and that the mechanism by 
      which MDMA and METH decreases TPH activity differs.
FAU - Johnson, M
AU  - Johnson M
AD  - Department of Pharmacology and Toxicology, University of Utah, Salt Lake City.
FAU - Mitros, K
AU  - Mitros K
FAU - Stone, D M
AU  - Stone DM
FAU - Zobrist, R
AU  - Zobrist R
FAU - Hanson, G R
AU  - Hanson GR
FAU - Gibb, J W
AU  - Gibb JW
LA  - eng
GR  - DA 00869/DA/NIDA NIH HHS/United States
GR  - DA 04221/DA/NIDA NIH HHS/United States
GR  - MH 44454/MH/NIMH NIH HHS/United States
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  - 0 (Receptors, Dopamine)
RN  - 0 (Receptors, Dopamine D2)
RN  - 333DO1RDJY (Serotonin)
RN  - 44RAL3456C (Methamphetamine)
RN  - 4764-17-4 (3,4-Methylenedioxyamphetamine)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - 57WA9QZ5WH (Nimodipine)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - EE92BBP03H (Diltiazem)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - R7PLA2DM0J (Flunarizine)
SB  - IM
MH  - 3,4-Methylenedioxyamphetamine/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Brain/*drug effects/enzymology
MH  - Chromatography, High Pressure Liquid
MH  - Diltiazem/pharmacology
MH  - Drug Interactions
MH  - Enzyme Induction/drug effects
MH  - Flunarizine/*pharmacology
MH  - Hydroxyindoleacetic Acid/chemistry
MH  - Injections, Subcutaneous
MH  - Male
MH  - Methamphetamine/*pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine
MH  - Nimodipine/*pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, Dopamine/drug effects/metabolism
MH  - Receptors, Dopamine D2
MH  - Serotonin/chemistry
MH  - Tryptophan Hydroxylase/*biosynthesis/metabolism
EDAT- 1992/05/01 00:00
MHDA- 1992/05/01 00:01
CRDT- 1992/05/01 00:00
PHST- 1992/05/01 00:00 [pubmed]
PHST- 1992/05/01 00:01 [medline]
PHST- 1992/05/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1992 May;261(2):586-91.