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Effects of nimodipine on the amphetamine- and methamphetamine-induced decrease in tryptophan hydroxylase activity

K W Elkins1, J W Gibb, G R Hanson

  • 1Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.

European Journal of Pharmacology
|December 21, 1993
PubMed
Summary
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Nimodipine, a calcium channel blocker, potentiates the effects of amphetamine and methamphetamine on brain chemistry. This drug interaction increases stimulant concentrations in the brain, impacting tryptophan hydroxylase activity.

Area of Science:

  • Neuropharmacology
  • Biochemistry

Background:

  • Amphetamine and methamphetamine are psychostimulants known to affect neurotransmitter systems.
  • Tryptophan hydroxylase is a key enzyme in serotonin synthesis.
  • Nimodipine is a dihydropyridine calcium channel blocker.

Purpose of the Study:

  • To investigate the effects of nimodipine on amphetamine- and methamphetamine-induced changes in central tryptophan hydroxylase activity.
  • To determine if nimodipine alters the brain concentrations of amphetamine and methamphetamine.

Main Methods:

  • Rats received multiple injections of amphetamine or methamphetamine, with or without nimodipine.
  • Tryptophan hydroxylase activity was measured in hippocampal and striatal tissues.
  • Drug concentrations in plasma and brain tissue were quantified.

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Main Results:

  • Nimodipine potentiated the decrease in hippocampal tryptophan hydroxylase activity induced by amphetamine and methamphetamine.
  • Nimodipine significantly increased hippocampal and striatal concentrations of amphetamine and methamphetamine.
  • Striatal tryptophan hydroxylase activity was not significantly affected by nimodipine coadministration.

Conclusions:

  • Nimodipines interaction with amphetamine and methamphetamine alters drug distribution.
  • The potentiation of decreased hippocampal tryptophan hydroxylase activity is linked to increased cerebral stimulant concentrations.
  • These findings highlight a potential drug interaction with implications for stimulant use and treatment.