methadone brands

Molecular formula: C21H27NO

Methadone is a synthetic opioid analgesic with full agonist activity at the µ-opioid receptor. While agonism of the µ-opioid receptor is the primary mechanism of action for the treatment of pain, methadone also acts as an agonist of κ- and σ-opioid receptors within the central and peripheral nervous systems. Interestingly, methadone differs from [morphine] (which is considered the gold standard reference opioid) in its antagonism of the N-methyl-D-aspartate (NMDA) receptor and its strong inhibition of serotonin and norepinephrine uptake, which likely also contributes to its antinociceptive activity. Methadone is administered as a 50:50 racemic mixture of (R)- and (S)-stereoisomers, with (R)-methadone demonstrating ~10-fold higher affinity and potency for the µ-opioid receptor than the (S) stereoisomer. The analgesic activity of the racemate is almost entirely due to the (R)-isomer, while the (S)-isomer lacks significant respiratory depressant activity but does have antitussive effects. While methadone shares similar effects and risks of other opioids such as [morphine], [hydromorphone], [oxycodone], and [fentanyl] it has a number of unique pharmacokinetic and pharmacodynamic properties that distinguish it from them and make it a useful agent for the treatment of opioid addiction. For example, methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Methadone hydrochloride is a mu-agonist; ... . Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone's efficacy is unknown. Methadone activates opioid receptors to increase a potassium conductance mediated by G-protein coupled, inwardly rectifying, potassium (K(IR) 3) channels. Methadone also blocks K(IR) 3 channels and NMDA receptors. However, the concentration dependence and stereospecificity of receptor activation and channel blockade by methadone on single neurons has not been characterized. Intracellular and whole cell recording were made from locus coeruleus neurons in brain slices and the activation of mu-opioid receptors and blockade of K(IR) 3 and NMDA channels with l- and d-methadone was examined. The potency of l-methadone, measured by the amplitude of hyperpolarization was 16.5-fold higher than with than d-methadone. A maximum hyperpolarization was caused by both enantiomers (~30 mV), however, the maximum outward current measured with whole cell voltage-clamp recording was smaller than the current induced by [Met](5) enkephalin. The K(IR) 3 conductance induced by activation of a(2) -adrenoceptors was decreased with high concentrations of l- and d-methadone (10-30 uM). In addition, methadone blocked the resting inward rectifying conductance (K(IR) ). Both l- and d-methadone blocked the NMDA receptor-dependent current. The block of NMDA receptor-dependent current was voltage dependent suggesting that methadone acted as a channel blocker. Methadone activated mu-opioid receptors at low concentrations in a stereospecific manner. K(IR) 3 and NMDA receptor channel block was not stereospecific and required substantially higher concentrations. The separation in the concentration range suggests that the activation of mu-opioid receptors rather than the channel blocking properties mediate both the therapeutic and toxic actions of methadone. Opioid agonist, analgesic. Action of methadone is to bind to mu-opiate and kappa-opiate receptors on nerves and inhibit release of neurotransmitters involved with transmission of pain stimuli (such as Substance P). Methadone also may antagonize NMDA (n-methyl D-asparate) receptors, which may contribute to the analgesic effect, decrease adverse CNS effects, and inhibit tolerance. ...

Source: PubChem (NCBI) · compound 4095