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Pharmacological effects and tissue concentrations of amphetamine in rats pretreated with diethyldithiocarbamate (DDC), a dopamine-β-hydroxylase inhibitor

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Summary

Diethyldithiocarbamate (DDC), 400 mg kg−1,s. c., given 1 hour or 16 hours before administration of (+)-amphetamine sulphate, 4 mg kg−1, i. p., increased the tissue concentrations and reduced the rates of elimination of amphetamine in brain, plasma, lung, kidney and liver, and this was probably due to inhibition of amphetaminep-hydroxylation. Concomitantly, there was a prolongation of two pharmacological effects of the stimulanti. e. hyperthermia and motor hyperactivity, in similarly treated rats. However, a hypothermic effect of DDC itself initially counteracted the hyperthermic response to amphetamine, indicating a dual interaction between the two drugs. The multiple biochemical actions of DDC and similar chemical agents seriously confound the interpretation of the results when using these dopamine (β-hydroxylase inhibitors,e. g. as pharmacological tools in elucidating the mechanism of action of other drugs.

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Correspondence to T. Lewander M.D..

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Jonsson, J., Lewander, T. Pharmacological effects and tissue concentrations of amphetamine in rats pretreated with diethyldithiocarbamate (DDC), a dopamine-β-hydroxylase inhibitor. European Journal of Drug Metabolism and Pharmacokinetics 1, 161–166 (1976). https://doi.org/10.1007/BF03189271

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Key-words

  • Diethyldithiocarbamate
  • amphetamine metabolism
  • drug interactions
  • body temperature
  • motor activity
  • rat