M100907 and BD 1047 Attenuate the Acute Toxic Effects of Methamphetamine.

M100907 and BD 1047 Attenuate the Acute Toxic Effects of Methamphetamine.
Neurotoxicology. 2019 Jun 01;:
Authors: Ray A, Canal CE, Ehlen JC, Rice KC, Murnane KS
Abstract
There are no Food and Drug Administration approved pharmacotherapies for methamphetamine (METH) overdose, thus identifying novel drug targets to prevent this devastating adverse event is a public-health imperative. Previous research suggests that serotonin and sigma receptors may contribute to the adverse effects of METH. The present study assessed whether pretreatment with the 5-HT2A receptor antagonist M100907 or the sigma 1 (σ1) receptor antagonist BD 1047 attenuated METH-induced lethality, hyperthermia, convulsions, and seizures. Male Swiss Webster mice received intraperitoneal injections of M100907 (1 and 10 mg/kg), BD 1047 (10 mg/kg), or a combination of M100907 (1 mg/kg) and BD 1047 (10 mg/kg) prior to treatment with METH (78 mg/kg). Convulsions and lethality were assessed by observation, core body temperature was assessed by surgically implanted telemetric probes, and seizures were assessed by electroencephalography. M100907 reduced METH-elicited lethality from 67% to 33%, BD1047 reduced METH-elicited lethality from 67% to 50%, and combined administration of both agents eliminated lethality in all mice tested. Similarly, both agents and their combination reduced METH-elicited seizures and convulsions. None of the treatments decreased METH-induced h...

Source: Neurotoxicology - May 31, 2019 Category: Neurology Authors: Ray A, Canal CE, Ehlen JC, Rice KC, Murnane KS Tags: Neurotoxicology Source Type: research