Are Histamine H3 Antagonists the Definitive Treatment for Acute Methamphetamine Intoxication?

Abstract

Methamphetamine (METH) is classified as a Schedule II stimulant drug under the United Nations Convention on Psychotropic Substances of 1971. METH and other amphetamine analogues (AMPHs) are powerful addictive drugs. Treatments are needed to treat the symptoms of METH addiction, chronic METH use, and acute METH overdose. No effective treatment for METH abuse has been established because alterations of brain functions under the excessive intake of abused drug intake are largely irreversible due in part to brain damage that occurs in the course of chronic METH use. Modulation of brain histamine neurotransmission is involved in several neuropsychiatric disorders, including substance use disorders. This review discusses the possible mechanisms underlying the therapeutic effects of histamine H3 receptor antagonists on symptoms of methamphetamine abuse. Treatment of mice with centrally acting histamine H3 receptor antagonists increases hypothalamic histamine contents and reduces high-dose METH effects while potentiating lowdose effects via histamine H3 receptors that bind released histamine. On the basis of experimental evidence, it is hypothesized that histamine H3 receptors may be an effective target for the treatment METH use disorder or other adverse effects of chronic METH use.