Drug interaction between methamphetamine and antihistamines: behavioral changes and tissue concentrations of methamphetamine in rats.
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.
Okuda
Tomohiro
T
Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Ito
Yukiko
Y
Nakagawa
Naoto
N
Hishinuma
Takanori
T
Tsukamoto
Hiroki
H
Iwabuchi
Kentaro
K
Watanabe
Takehiko
T
Kitaichi
Kiyoyuki
K
Goto
Junichi
J
Yanai
Kazuhiko
K
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
D000697:Central Nervous System Stimulants; D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D008694:Methamphetamine