Efficacy of D,L-methadone in the treatment of glioblastoma in vitro

CNS Oncol. 2018 Jul 1;7(3):CNS18. doi: 10.2217/cns-2018-0006. Epub 2018 Jun 19.

Abstract

Aim: Recently, D,L-methadone has been put forward as adjuvant treatment in glioblastoma (GBM).

Methods: We analyzed the μ-opioid receptor expression in a set of GBM cell lines and investigated the efficacy of D,L-methadone alone and in combination with temozolomide (TMZ). Results & conclusion: Expression of the μ-opioid receptor was similar in the tested cell lines. High concentrations of D,L-methadone induced apoptosis in all cell lines and showed treatment interaction with TMZ. However, in lower dosages, reflecting clinically attainable concentrations, D,L-methadone alone showed no efficacy, and induced even higher proliferation in one specific cell line. Also, no interaction with TMZ was observed. These results suggest caution to the premature use of D,L-methadone in the treatment of GBM patients.

Keywords: adjuvant treatment; glioblastoma; methadone; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology*
  • Humans
  • Male
  • Methadone / pharmacology
  • Methadone / therapeutic use*
  • Middle Aged
  • Receptors, Opioid, mu / metabolism
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use

Substances

  • Analgesics, Opioid
  • Antineoplastic Agents, Alkylating
  • Receptors, Opioid, mu
  • Methadone
  • Temozolomide