levomethadyl acetate

Trade name: orlaam

Small moleculeapprovedOrphan Drug FDA

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

Phase 1
1
Phase 2
2
Phase 3
0
Phase 4
1

Earliest trial started Jun 1, 1991 (NCT00000356)

Timeline

1980s

  1. Jan 24, 1985

    Orphan Drug Designation

1990s

  1. Jan 1, 1991

    Earliest Phase 2 Sponsor(trial)

  2. Jul 9, 1993

    Roxane Laboratories — Earliest FDA Approval

  3. Jul 9, 1993

    Roxane Laboratories — NDA Secondary Org

  4. Jul 9, 1993

    Roxane Laboratories — NDA Organization

  5. Jul 9, 1993

    Boehringer Ingelheim — NDA Secondary Org

2010s

  1. Jan 1, 2013

    Earliest Phase 1 Sponsor(trial)

Indications

Mechanism of action

Approval history

  • approvedPriority reviewJul 9, 1993

Chemistry & pharmacology

Loading structure…

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

Prodrug

Sources

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 IDPhaseStart dateSponsor(s)
NCT01935830Early Phase 1 (Phase 1)Aug 1, 2013Washington University in St. Louis
NCT00218127Phase 2Nov 1, 2001National Institute on Drug Abuse (NIDA), University of Texas at Houston
NCT00000300Phase 4Mar 1, 1995Friends Research Institute, Inc., National Institute on Drug Abuse (NIDA)
NCT00000356Phase 2Jun 1, 1991National Institute on Drug Abuse (NIDA), University of Pennsylvania
Showing 4 of 4 trials
Page 1 / 1

Organizations

Research & Development (5)

OrganizationOrg typeTrialsAs lead sponsorPhasesEarliest year
National Institute on Drug Abuse (NIDA)Government3321991
Friends Research Institute, Inc.Academic/Hospital1011995
University of PennsylvaniaAcademic/Hospital1011991
University of Texas at HoustonAcademic/Hospital1012001
Washington University in St. LouisAcademic/Hospital1112013
5 organizations
Page 1 / 1

Marketing (3)

OrganizationOrg typeRelationshipDate
Boehringer IngelheimFor profitNDA2Jul 9, 1993
Roxane LaboratoriesFor profitNDA2Jul 9, 1993
Roxane LaboratoriesFor profitNDAJul 9, 1993