levomethadyl acetate
Trade name: orlaam
Approved
Jul 9, 1993
Levomethadyl acetate (LAAM) is a synthetic opioid agonist with actions qualitatively similar to morphine (a prototypic mu agonist) and affecting the central nervous system (CNS) and smooth muscle. Principal actions include analgesia and sedation. Tolerance to these effects develops with repeated use. An abstinence syndrome generally occurs upon cessation of chronic administration similar to that observed with other opiates, but with slower onset, more prolonged course, and less severe symptoms. LAAM exerts its clinical effects in the treatment of opiate abuse through two mechanisms. First, LAAM cross-substitutes for opiates of the morphinetype, suppressing symptoms of withdrawal in opiate-dependent individuals. Second, chronic oral administration of LAAM can produce sufficient tolerance to block the subjective “high” of usual doses of parenterally administered opiates. Since the introduction of levomethadyl in 1995, the manufacturer has received increasing reports of severe cardiac-related adverse events, including QT interval prolongation, Torsades de Pointes and cardiac arrest. Other cardiac-related adverse events have also been reported, including arrhythmias, syncope, and angina. These events led to the removal of levomethadyl from the European market in March 2001. A very small number of patients may benefit from levomethadyl, but the risk of continued distribution and use no longer outweighs the overall benefits. — NCATS
Clinical trial activity
4 trials · 5 clinical orgs · 2 marketing orgs
Earliest trial started Jun 1, 1991 (NCT00000356)
Timeline
1980s
- Jan 24, 1985
Orphan Drug Designation
1990s
- Jan 1, 1991
Earliest Phase 2 Sponsor(trial)
- Jul 9, 1993
Roxane Laboratories — Earliest FDA Approval
- Jul 9, 1993
Roxane Laboratories — NDA Secondary Org
- Jul 9, 1993
Roxane Laboratories — NDA Organization
- Jul 9, 1993
Boehringer Ingelheim — NDA Secondary Org
2010s
- Jan 1, 2013
Earliest Phase 1 Sponsor(trial)
Indications
Approved for
Mechanism of action
- Mu opioid receptorAGONIST
OPRM agonist
Approval history
- approvedPriority reviewJul 9, 1993
Chemistry & pharmacology
SMILES
CC[C@H](OC(C)=O)C(C[C@H](C)N(C)C)(c1ccccc1)c1ccccc1- Mol. weight
- 353.51 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- No
- Chirality
- Single Stereoisomer
- Inorganic
- No
- Polymer
- No
- Delivery
- Oral
- Availability
- Discontinued
Oral
Yes
Parenteral
No
Topical
No
Sources
- ChEMBLCHEMBL1514 ↗
- WikipediaLevacetylmethadol ↗
- NCATSR3B637Y991 ↗
- ChEMBLCHEMBL1200817 ↗
Also known as
- 1-alpha-acetylmethadol
- 1-alpha-acetylmethadol
- (1s,4s)-4-(dimethylamino)-1-ethyl-2,2-diphenylpentyl acetate
- (1s,4s)-4-(dimethylamino)-1-ethyl-2,2-diphenylpentyl acetate
- (-)-alpha-acetylmethadol
- (-)-alpha-acetylmethadol
- laam
- laam
- laam
- l-alpha-acetylmethadol
- l-alpha-acetylmethadol
- levacetilmetadol
- levacetilmetadol
- levacetylmethadol
- levacetylmethadol
- levacetylmethadol
- levacetylmethadol
- levacetylmethadol
- levacetylmethadol hydrochloride
- levacetylmethadolum
- levacetylmethadolum
- levoacetyl methadol
- levo-alpha-acetylmethadol
- levo-alpha-acetylmethadol
- levomethadyl
- levomethadyl
- levomethadyl
- levomethadyl
- levo-methadyl acetate
- levo-methadyl acetate
- levomethadyl acetate
- levomethadyl acetate
- levomethadyl acetate
- levomethadyl acetate
- levomethadyl acetate
- levomethadyl acetate
- levomethadyl acetate
- levomethadyl acetate
- levomethadyl acetate hcl
- levomethadyl acetate hcl
- levomethadyl acetate hcl
- levomethadyl acetate hydrochloride
- levomethadyl acetate hydrochloride
- levomethadyl acetate hydrochloride
- levomethadyl acetate hydrochloride
- levomethadyl acetate hydrochloride
- levomethadyl acetate hydrochloride
- levo-α-acetylmethadol
- levo-α-acetylmethadol
- mk-790
- mk-790
- orlaam
- orlaam
- orlaam
- orlaam
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT01935830 | Early Phase 1 (Phase 1) | Aug 1, 2013 | Washington University in St. Louis |
| NCT00218127 | Phase 2 | Nov 1, 2001 | National Institute on Drug Abuse (NIDA), University of Texas at Houston |
| NCT00000300 | Phase 4 | Mar 1, 1995 | Friends Research Institute, Inc., National Institute on Drug Abuse (NIDA) |
| NCT00000356 | Phase 2 | Jun 1, 1991 | National Institute on Drug Abuse (NIDA), University of Pennsylvania |
Organizations
Research & Development (5)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| National Institute on Drug Abuse (NIDA) | Government | 3 | 3 | 2 | 1991 |
| Friends Research Institute, Inc. | Academic/Hospital | 1 | 0 | 1 | 1995 |
| University of Pennsylvania | Academic/Hospital | 1 | 0 | 1 | 1991 |
| University of Texas at Houston | Academic/Hospital | 1 | 0 | 1 | 2001 |
| Washington University in St. Louis | Academic/Hospital | 1 | 1 | 1 | 2013 |
Marketing (3)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Boehringer Ingelheim | For profit | NDA2 | Jul 9, 1993 |
| Roxane Laboratories | For profit | NDA2 | Jul 9, 1993 |
| Roxane Laboratories | For profit | NDA | Jul 9, 1993 |