Drug interaction between methamphetamine and antihistamines: Behavioral changes and tissue concentrations of methamphetamine in rats

Tomohiro Okuda, Yukiko Ito, Naoto Nakagawa, Takanori Hishinuma, Hiroki Tsukamoto, Kentaro Iwabuchi, Takehiko Watanabe, Kiyoyuki Kitaichi, Junichi Goto, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Methamphetamine is a psychomotor stimulant, whereas first generation antihistamines cause sedation. Several studies have demonstrated that first generation antihistamines potentiate methamphetamine-induced psychomotor activation and two possible mechanisms have been postulated. One is blockage of the central histaminergic neuron system and the other is inhibition of dopamine reuptake. However, the exact mechanism is still controversial. In this study, we examined in behavioral tests the effects of selected antihistamines on methamphetamine-induced psychomotor activation in rats, and measured plasma and brain tissue concentrations of methamphetamine. We found that some antihistamines significantly potentiate methamphetamine-induced psychomotor activation in rats and that plasma and brain tissue concentrations of methamphetamine in rats treated with methamphetamine in combination with d-chlorpheniramine were markedly higher than those in rats treated with methamphetamine alone. These results suggest that the potentiating effects of antihistamines are due to not only central effects but also the alteration of the pharmacokinetics of methamphetamine.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalEuropean Journal of Pharmacology
Volume505
Issue number1-3
DOIs
Publication statusPublished - 2004 Nov 28

Keywords

  • Antihistamine
  • Locomotor activity
  • Methamphetamine
  • Methamphetamine concentration
  • Prepulse inhibition

ASJC Scopus subject areas

  • Pharmacology

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