Brain Histamine N-Methyltransferase as a Possible Target of Treatment for Methamphetamine Overdose

Junichi Kitanaka; Nobue Kitanaka; F. Scott Hall; George R. Uhl; Motohiko Takemura

doi:10.33393/dti.2016.1423

Authors

Junichi Kitanaka Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
Nobue Kitanaka Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
F. Scott Hall Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
George R. Uhl New Mexico VA Healthcare System/BRINM, Albuquerque, NM, USA
Motohiko Takemura Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.

DOI:

https://doi.org/10.33393/dti.2016.1423

Keywords:

methamphetamine, overdose, Stereotyped behavior, histamine N-methyltransferase, brain histaminergic system, metoprine

Abstract

Stereotypical behaviors induced by methamphetamine (METH) overdose are one of the overt symptoms of METH abuse, which can be easily assessed in animal models. Currently, there is no successful treatment for METH overdose. There is increasing evidence that elevated levels of brain histamine can attenuate METH-induced behavioral abnormalities, which might therefore constitute a novel therapeutic treatment for METH abuse and METH overdose. In mammals, histamine N-methyltransferase (HMT) is the sole enzyme responsible for degrading histamine in the brain. Metoprine, one of the most potent HMT inhibitors, can cross the blood–brain barrier and increase brain histamine levels by inhibiting HMT. Consequently, this compound can be a candidate for a prototype of drugs for the treatment of METH overdose.