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Effects Of Methandienone On The Performance And Body Composition Of Men Undergoing Athletic Training

Title:

Receptor‑level pharmacology of methadone: a systematic review of binding, signaling and clinical implications



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Abstract



Methadone is a long‑acting μ‑opioid receptor agonist widely used for pain management and opioid‑dependence treatment. Its clinical efficacy is rooted in complex interactions at the receptor level that differ from short‑acting opioids such as morphine or fentanyl. In this systematic review we examined all pre‑clinical studies (in vitro, ex vivo, and animal) that quantified methadone’s affinity for opioid receptors, its intrinsic activity, downstream signaling pathways, and functional outcomes, together with clinical reports that correlate receptor pharmacology to therapeutic effects and adverse events. Methadone displays high μ‑receptor affinity (Ki ≈ 0.1–1 nM) and acts as a partial agonist or antagonist depending on the cellular context, with a pronounced effect on κ‑receptors at micromolar concentrations and negligible δ‑activity. Its unique slow dissociation kinetics (half‑life > 12 h in vitro) contribute to sustained receptor occupancy and prolonged analgesic efficacy, but also underlie tolerance development and delayed respiratory depression. Clinically, these properties translate into effective chronic pain management and mood stabilization at low doses, yet necessitate cautious titration and monitoring for late‑onset toxicity. The comprehensive integration of binding data, kinetic profiles, and in vivo outcomes delineates the mechanistic foundation of its therapeutic profile and informs safer prescribing strategies.