Brands, Medical Use, Clinical Data
- Opiate Agonists
Brands / Synonyms
(+/-)-Methadone; (+/-)-Methadone hydrochloride; (+/-)-Tussal; Adanon; Adanon hydrochloride; Adolan; Algidon; Algolysin; Algovetin; Althose hydrochloride; Amidon; Amidone; Biscuits; Butalgin; Depridol; Diaminon; Diaminon hydrochloride; dl-Methadone
; DL-Methadone hydrochloride; Dollies; Dolly; Dolofin hydrochloride; Dolohepton; Dolophin; Dolophin hydrochloride; Dolophine; Dolophine HCL; Fenadon; Fenadone; Heptadon; Heptadone; Heptanon; Ketalgin; Ketalgin hydrochloride; Mecodin; Medicine; Mephenon; Meth; Methadon; Methadone; Methadone HCL; Methadone HCL Intensol; Methadone hydrochloride; Methadone hydrochloride dl-; Methadone M; Methadose; Methaquaione; Miadone; Moheptan; Phenadone; Phenadone hydrochloride; Physeptone; Polamidon; Polamidone; Racemic methadone; Racemic methadone hydrochloride; Tussol:; Westadone
For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain
Methadone is a synthetic opioid analgesic with multiple actions quantitatively similar to those at morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, Methadone is more active and more toxic than morphine. Methadone is indicated for relief of severe pain, for detoxification treatment of narcotic addiction, and for temporary maintenance treatment of narcotic addiction. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. The 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.
Mechanism of Action
Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Methadone's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability. Methadone has a unique affinity for the NMDA brain receptor. It is believed that NMDA (N-methyl-D-aspartic acid) may regulate psychic dependence and tolerance by exhibiting opioid antagonist-like activity.
Biotrnasformation / Drug Metabolism
Hypersensitivity to methadone.
Interaction with Pentazocine
Patients who are addicted to heroin or who are on the methadone maintenance program may experience withdrawal symptoms when given pentazocine.
Interaction with Rifampin
The concurrent administration of rifampin may possibly reduce the blood concentration of methadone. The mechanism by which rifampin may decrease blood concentrations of methadone is not fully understood although enhanced microsomal drug-metabolized enzymes may influence drug disposition.
Interaction with Monoamine Oxidase (MAO) Inhibitors
Therapeutic doses of meperidine have precipitated severe reactions in patients concurrently receiving monoamine oxidase inhibitors or those who have received such agents within 14 days. Similar reactions thus far have not been reported with methadone; but if the use of methadone is necessary in such patients, a sensitivity test should be performed in which repeated small incremental doses are administered over the course of several hours while the patient's condition and vital signs are under careful observation.
Interaction with Other Central-Nervous-Systern Depressants
Methadone should be used with caution and in reduced dosage in patients who are concurrently receiving other narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative-hypnotics, tricyclic antidepressants, and other CNS depressants (including alcohol). Respiratory depression, hypotension, and profound sedation or coma may result.