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

• Published in: European journal of pharmacology Vol. 505; no. 1; pp. 135 - 144
• Main Authors: Okuda, Tomohiro, Ito, Yukiko, Nakagawa, Naoto, Hishinuma, Takanori, Tsukamoto, Hiroki, Iwabuchi, Kentaro, Watanabe, Takehiko, Kitaichi, Kiyoyuki, Goto, Junichi, Yanai, Kazuhiko
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.11.2004; Elsevier
• Subjects: Animals; Antihistamine; Area Under Curve; Behavior, Animal - drug effects; Biological and medical sciences; Brain - metabolism; Central Nervous System Stimulants - blood; Central Nervous System Stimulants - pharmacokinetics; Central Nervous System Stimulants - pharmacology; Chlorpheniramine - pharmacology; Drug Interactions; Histamine H1 Antagonists - pharmacology; Locomotor activity; Male; Medical sciences; Methamphetamine; Methamphetamine - blood; Methamphetamine - pharmacokinetics; Methamphetamine - pharmacology; Methamphetamine concentration; Motor Activity - drug effects; Neural Inhibition - drug effects; Pharmacology. Drug treatments; Prepulse inhibition; Rats; Rats, Sprague-Dawley; Time Factors; Tissue Distribution; Methamphetamine concentration; Antihistamine; Locomotor activity; Methamphetamine; Prepulse inhibition; Amphetamine derivatives; Rat; CNS stimulant; Psychotropic; Rodentia; Metamfetamine; Sympathomimetic; Antihistaminic; Vertebrata; Mammalia; Animal; Drug interaction; Behavior
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.10.022

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.