title: Drug interaction between methamphetamine and antihistamines: behavioral changes and tissue concentrations of methamphetamine in rats.
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.
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Okuda
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakagawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Hishinuma
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwabuchi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Kitaichi
authors.forename: Junichi
authors.initials: J
authors.lastname: Goto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology; D004347:Drug Interactions; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000697:Central Nervous System Stimulants; D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D008694:Methamphetamine