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. 2004 Nov 28;505(1-3):135-44.
doi: 10.1016/j.ejphar.2004.10.022.

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

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

Tomohiro Okuda et al. Eur J Pharmacol. .

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.

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