Levacetylmethadol
Encyclopedia
Levacetylmethadol levomethadyl acetate (USAN
), Orlaam (trade name) or levo-α-acetylmethadol (LAAM) is a synthetic opioid
similar in structure to methadone
. It has a long duration of action due to its active metabolites. It was approved in 1993 by the U.S. Food and Drug Administration for use in the treatment of opioid dependence. In 2001, Orlaam was removed from the European market due to reports of life threatening ventricular rhythm disorders. In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.
is indicated as a second-line treatment for the treatment and management of opioid dependence if patients fail to respond to drugs like methadone
or buprenorphine
. Before August, 1993 LAAM
was classified as a schedule I drug in the United States. LAAM
is not approved for use in Canada
.
. It also acts as a potent, noncompetitive α3β4
neuronal nicotinic acetylcholine receptor
antagonist
.
Levomethadyl acetate is the levo isomer of α-methadyl acetate. The dextro isomer, alphacetylmethadol
, is more potent but shorter acting. The levo isomer is also less toxic with an in mice of 110 mg/kg s.c. and 172.8 mg/kg orally as opposed to s of 61 mg/kg s.c. and 118.3 mg/kg orally for dl-α-methadyl acetate. It has a melting point
of 215 °C and a molecular weight of 353.50. β-methadyl acetate also exists, however it is more toxic and less active than α-methadyl acetate and has no current medical use.
Levomethadyl acetate undergoes extensive first-pass metabolism
to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. These metabolites are more potent than the parent drug.
solution
of levomethadyl acetate hydrochloride
at a concentration of 10 mg/mL in bottles of 120 and 500 mL under the brand name Orlaam. The first dose of LAAM for patients who have not started treatment with methadone
is 20–40 mg. The first dose for patients who have been receiving methadone
will be a little higher than the amount of methadone that was being taken every day, but not more than 120 mg. Afterwards, the dosage may be adjusted as needed. Unlike methadone, which requires daily administration, LAAM is administered two to three times a week.
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...
), Orlaam (trade name) or levo-α-acetylmethadol (LAAM) is a synthetic opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
similar in structure to methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
. It has a long duration of action due to its active metabolites. It was approved in 1993 by the U.S. Food and Drug Administration for use in the treatment of opioid dependence. In 2001, Orlaam was removed from the European market due to reports of life threatening ventricular rhythm disorders. In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US.
Indications
LAAMLââm
Lââm is a French female singer of Tunisian descent. She has sold more than 500,000 albums and more than 2 million singles.-Biography:...
is indicated as a second-line treatment for the treatment and management of opioid dependence if patients fail to respond to drugs like methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
or buprenorphine
Buprenorphine
Buprenorphine is a semi-synthetic opioid that is used...
. Before August, 1993 LAAM
Lââm
Lââm is a French female singer of Tunisian descent. She has sold more than 500,000 albums and more than 2 million singles.-Biography:...
was classified as a schedule I drug in the United States. LAAM
Lââm
Lââm is a French female singer of Tunisian descent. She has sold more than 500,000 albums and more than 2 million singles.-Biography:...
is not approved for use in Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
.
Chemistry and pharmacology
Levacetylmethadyl acts as a mu-opioid receptor agonistAgonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
. It also acts as a potent, noncompetitive α3β4
Alpha-3 beta-4 nicotinic receptor
The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor, is a type of nicotinic acetylcholine receptor, consisting of α3 and β4 subunits. It is located in the brain, where activation yields post- and presynaptic excitation....
neuronal nicotinic acetylcholine receptor
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
antagonist
Nicotinic antagonist
A nicotinic antagonist is a type of anticholinergic that inhibits the action at nicotinic acetylcholine receptors. These compounds are mainly used for peripheral muscle paralysis in surgery, but some centrally acting compounds such as bupropion, mecamylamine, and 18-methoxycoronaridine block...
.
Levomethadyl acetate is the levo isomer of α-methadyl acetate. The dextro isomer, alphacetylmethadol
Alphacetylmethadol
Alphacetylmethadol is a synthetic opioid. It is the enantiomer of levacetylmethadol. In the United States, it is a Schedule I drug under the Controlled Substances Act....
, is more potent but shorter acting. The levo isomer is also less toxic with an in mice of 110 mg/kg s.c. and 172.8 mg/kg orally as opposed to s of 61 mg/kg s.c. and 118.3 mg/kg orally for dl-α-methadyl acetate. It has a melting point
Melting point
The melting point of a solid is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends on pressure and is usually specified at standard atmospheric pressure...
of 215 °C and a molecular weight of 353.50. β-methadyl acetate also exists, however it is more toxic and less active than α-methadyl acetate and has no current medical use.
Levomethadyl acetate undergoes extensive first-pass metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
to the active demethylated metabolite nor-LAAM, which is further demethylated to a second active metabolite, dinor-LAAM. These metabolites are more potent than the parent drug.
Dosing
LAAM is used as an oralMouth
The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
solution
Solution
In chemistry, a solution is a homogeneous mixture composed of only one phase. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvent does the dissolving.- Types of solutions :...
of levomethadyl acetate hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
at a concentration of 10 mg/mL in bottles of 120 and 500 mL under the brand name Orlaam. The first dose of LAAM for patients who have not started treatment with methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
is 20–40 mg. The first dose for patients who have been receiving methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
will be a little higher than the amount of methadone that was being taken every day, but not more than 120 mg. Afterwards, the dosage may be adjusted as needed. Unlike methadone, which requires daily administration, LAAM is administered two to three times a week.
External links
- LAAM Drug Information
- RxList Monograph for Orlaam
- DrugBank: Levomethadyl Acetate
- http://cat.inist.fr/?aModele=afficheN&cpsidt=2706063
- http://cat.inist.fr/?aModele=afficheN&cpsidt=2390242