Methadone

Generic Name
Methadone
Brand Names
Diskets, Dolophine, Metadol, Metadol-D, Methadose
Drug Type
Small Molecule
Chemical Formula
C21H27NO
CAS Number
76-99-3
Unique Ingredient Identifier
UC6VBE7V1Z
Background

Methadone is a potent synthetic analgesic that works as a full µ-opioid receptor (MOR) agonist and N-methyl-d-aspartate (NMDA) receptor antagonist. As a full MOR agonist, methadone mimics the natural effects of the body's opioids, endorphins, and enkephalins through the release of neurotransmitters involved in pain transmission. It also has a number of unique characteristics that have led to its increased use in the last two decades; in particular, methadone has a lower risk of neuropsychiatric toxicity compared to other opioids (due to a lack of active metabolites), minimal accumulation in renal failure, good bioavailability, low cost, and a long duration of action.

Due to its unique mechanism of action, methadone is particularly useful for the management of hard to treat pain syndromes such as neuropathic pain and cancer pain requiring higher and more frequent doses of shorter-acting opioids. Compared with morphine, the gold standard reference opioid, methadone also acts as an agonist of κ- and σ-opioid receptors, as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, and as an inhibitor of serotonin and norepinephrine uptake. Specifically by inhibiting the NMDA receptor, methadone dampens a major excitatory pain pathway within the central nervous system. Compared to other opioids, methadone's effects on NMDA inhibition may explain it's improved analgesic efficacy and reduced opioid tolerance.

Methadone shares similar effects and risks of other opioids such as morphine, hydromorphone, oxycodone, and fentanyl. However, it also has a unique pharmacokinetic profile. Compared with short-acting and even extended-release formulations of morphine, methadone displays a comparatively longer duration of action and half-life. These effects make methadone a good option for the treatment of severe pain and addiction as fewer doses are needed to maintain analgesia and prevent opioid withdrawal symptoms. However, methadone also has an unpredictable half-life with interindividual variability, which leads to an unpredictable risk of respiratory depression and overdose when initiating or titrating therapy.

Overall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis, sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and constipation. At higher doses, methadone use can result in respiratory depression, overdose, and death.

Treatment of opioid addiction with methadone, buprenorphine, or slow-release oral morphine (SROM) is termed Opioid Agonist Treatment (OAT) or Opioid Substitution Therapy (OST). The intention of substitution of illicit opioids with the long-acting opioids used in OAT is to prevent withdrawal symptoms for 24-36 hours following dosing to ultimately reduce cravings and drug-seeking behaviours. Use of OAT is also intended to lead to social stabilization by reducing crime rates, incarceration, use of illicit opioids such as heroin or fentanyl, and ultimately marginalization. Illegally purchased opioids present many other harms in addition to overdose as they can be injected and may be laced with other substances that increase the risk of harm or overdose. Provision of OAT is often combined with education about harm reduction including use of clean needles and injection supplies in an effort to reduce the risks associated with injection drug use such as contraction of HIV and Hepatitis C and other complications including skin infections, abscesses, or endocarditis.

Indication

Methadone is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatment options are inadequate. It's recommended that use is reserved for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Methadone is also indicated for detoxification treatment of opioid addiction (heroin or other morphine-like drugs), and for maintenance substitution treatment for opioid dependence in adults in conjunction with appropriate social and medical services.

Associated Conditions
Opioid Addiction, Severe Pain
Associated Therapies
Opioid Detoxification, Maintenance therapy

HIV Risk Reduction in Subutex Injectors in Tbilisi

First Posted Date
2010-05-26
Last Posted Date
2016-08-19
Lead Sponsor
University of Pennsylvania
Target Recruit Count
68
Registration Number
NCT01131273
Locations
🇬🇪

Union Alternative Georgia, Tbilisi, Georgia

Methadone Versus Placebo in Spine Fusion

Not Applicable
Withdrawn
Conditions
Interventions
First Posted Date
2010-05-18
Last Posted Date
2015-04-22
Lead Sponsor
Northwestern University
Registration Number
NCT01125059
Locations
🇺🇸

Northwestern Memorial Hospital, Chicago, Illinois, United States

Estimate The Effect Of Lersivirine On The Pharmacokinetics Of S- And R-Methadone

First Posted Date
2010-04-07
Last Posted Date
2010-08-30
Lead Sponsor
Pfizer
Target Recruit Count
13
Registration Number
NCT01099748
Locations
🇺🇸

Pfizer Investigational Site, Philadelphia, Pennsylvania, United States

Measuring the Amount of Methadone or Morphine in the Blood of Neonates, Infants & Children After Cardiac Surgery.

Phase 1
Completed
Conditions
Interventions
First Posted Date
2010-03-29
Last Posted Date
2017-09-18
Lead Sponsor
Stanford University
Target Recruit Count
47
Registration Number
NCT01094522
Locations
🇺🇸

University of Colorado, Denver, Colorado, United States

🇺🇸

Oregon Health & Sciences University, Portland, Oregon, United States

🇺🇸

Stanford University School of Medicine, Stanford, California, United States

Treatment for Opioid Dependent Offenders

First Posted Date
2010-03-08
Last Posted Date
2023-06-05
Lead Sponsor
University of Wisconsin, Madison
Target Recruit Count
16
Registration Number
NCT01082679
Locations
🇺🇸

University of Wisconsin - Madison, Madison, Wisconsin, United States

Morphine Slow-release Capsules in Substitution Therapy

First Posted Date
2010-03-02
Last Posted Date
2014-03-28
Lead Sponsor
Mundipharma Medical Company
Target Recruit Count
276
Registration Number
NCT01079117

Compare Methadone Combined With N-Acetyl-Cysteine (NAC) and Methadone Alone for Opioids Astaining

First Posted Date
2010-01-13
Last Posted Date
2010-01-14
Lead Sponsor
Taichung Veterans General Hospital
Target Recruit Count
60
Registration Number
NCT01047956
Locations
🇨🇳

Taichung Veterans General Hospital, Taichung City, Taiwan

Opiate Detoxification Using the Combined Hemoperfusion-hemodialysis

First Posted Date
2009-11-30
Last Posted Date
2009-11-30
Lead Sponsor
First People's Hospital of Foshan
Target Recruit Count
60
Registration Number
NCT01021566
Locations
🇨🇳

the First People's Hospital of Foshan, Foshan, Guangdong, China

QTc and Perceived Sleep Follow up Among Chronic Pain Patients With Opiate Medication

Not Applicable
Conditions
Interventions
First Posted Date
2009-10-21
Last Posted Date
2010-01-21
Lead Sponsor
Tel-Aviv Sourasky Medical Center
Target Recruit Count
100
Registration Number
NCT00999440
Locations
🇮🇱

Tel Aviv Sourasky Medical Center, Pain Medicine Unit, Tel Aviv, Israel

A Study to Investigate the Potential Interaction Between Telaprevir and Methadone, at Steady-State

Phase 1
Completed
Conditions
Interventions
First Posted Date
2009-07-07
Last Posted Date
2012-12-03
Lead Sponsor
Tibotec BVBA
Target Recruit Count
18
Registration Number
NCT00933283
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