The Sound of Evolution
Methadone
Mechanism of action:
Methadone is an opioid and a diphenylpropylamine derivative. Methadone acts as an agonist of the μ-opioid receptor. Upon binding, it inhibits adenylyl cyclase activity, lowers intracellular cAMP concentration, and suppresses presynaptic voltage-gated Ca²⁺ channels, thereby preventing calcium influx and reducing the release of pain-related neurotransmitters such as glutamate and substance P. At the same time, it activates postsynaptic K⁺ channels, promoting potassium efflux and leading to neuronal hyperpolarization.
Reference(s):
1. Kell MJ et al. (1994). Utilization of plasma and urine methadone concentrations to optimize treatment in maintenance clinics: I. Measurement techniques for a clinical setting. J Addict Dis.
2. Eap CB et al. (2002). Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet.
3. Joseph H et al. (2000). Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med.