Basic information Safety Supplier Related

(+/-)-METHADONE

Basic information Safety Supplier Related

(+/-)-METHADONE Basic information

Product Name:
(+/-)-METHADONE
Synonyms:
  • 6-Dimethyamino-4,4-diphenyl-heptan-3-one
  • DL-METHADONE
  • methadona
  • Methadone M
  • methadone(l)
  • methadonum(latin)
  • methadose
  • Phenadone
CAS:
76-99-3
MF:
C21H27NO
MW:
309.45
EINECS:
200-996-9
Mol File:
76-99-3.mol
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(+/-)-METHADONE Chemical Properties

Melting point:
78°
Boiling point:
449.71°C (rough estimate)
Density 
1.0350 (rough estimate)
refractive index 
1.5614 (estimate)
Flash point:
9℃
storage temp. 
−20°C
pka
pKa 8.25 (Uncertain)
EPA Substance Registry System
3-Heptanone, 6-(dimethylamino)-4,4-diphenyl- (76-99-3)
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Safety Information

Hazard Codes 
F,T
Risk Statements 
11-23/24/25-39/23/24/25
Safety Statements 
7-16-36/37-45
RIDADR 
UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany 
1
Hazardous Substances Data
76-99-3(Hazardous Substances Data)
Toxicity
LD50 oral in rat: 86mg/kg
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(+/-)-METHADONE Usage And Synthesis

Originator

Dolophine ,Lilly,US,1947

Uses

Analgesic (narcotic).

Definition

ChEBI: A ketone that is heptan-3-one substituted by a dimethylamino group at position 6 and two phenyl groups at position 4.

Definition

methadone: A synthetic opioid,C21H27NO, used medically as an analgesicfor chronic pains and also as asubstitute for heroin in the treatmentof addiction. Methadone is itselfaddictive and considerablequantities of ‘street’ methadone areused in the UK.

Manufacturing Process

Diphenylacetonitrile is condensed with 2-chloro-1-dimethylaminopropane to give 4-(dimethylamino)-2,2-diphenyl valeronitrile. It is then reacted with ethyl magnesium bromide and then hydrolyzed using HCl to give methadone hydrochloride.

brand name

Dolophine Hydrochloride (Roxane); Dolophine Hydrochloride (Xanodyne); Methadose (Mallinckrodt); Westadone (Sandoz).

Therapeutic Function

Narcotic analgesic

Biological Functions

Methadone (Dolophine) has an analgesic profile and potency similar to that of morphine but a longer duration of action and better oral bioavailability.The kinetic properties of methadone and its derivative, LAAM, have been shown to be useful in the treatment of opioid addiction. Methadone is a useful analgesic drug for the treatment of moderate to severe pain. Unlike morphine, it is generally not used epidurally because of its long duration of action. It is also rarely or never used in PCA systems or in pregnant women during labor. The side effects and signs of overdose following methadone administration are similar to those observed with morphine. Overdose is treated with naloxone. Clearance of methadone is via the urine and bile as the cyclic Ndemethylated drug. The ability to N-demethylate the drug decreases in elderly patients, prolonging the action of methadone. In such patients, dosing intervals should be longer than in younger patients. In addition, the pH of the urine has a major effect on clearance of the drug. Alkalinization of the urine or renal insufficiency decreases excretion of the drug.
Drug interactions and precautions for the use of methadone are similar to those of morphine. In addition, rifampicin and hydantoins markedly increase the metabolism of methadone and can precipitate withdrawal from methadone. Conversely, the tricyclic antidepressants and certain benzodiazepines can inhibit metabolism of methadone, thereby increasing accumulation of the drug, prolonging its half-life, and intensifying its side effects. Continuous dosing with methadone may lead to drug accumulation and to an increased incidence of side effects; methadone is generally not used for PCA. In pregnant heroin-addicted women, substitution of methadone for heroin has been shown to be associated with fewer low-birth-weight newborns and fewer learning and cognition problems later in the life of the child.

General Description

Methadone (Dolophine) is a synthetic opioid approved for analgesic therapy and for the maintenance and treatment of opioid addiction. Methadone is marketed as the racemate, although the opioid activity resides in the R-enantiomer (7–50 times more potent than the S-enantiomer). Methadone may only be dispensed for the treatment of opioid addiction by a program certified by the Federal Substance Abuse and Mental Health Services Administration.
Methadone is a μ-receptor agonist with complex and highly variable pharmacokinetic parameters. The major metabolic pathway of methadone metabolism is via Ndemethylation to an unstable product that spontaneously cyclizes to form the inactive 2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine (EDDP).

Pharmacology

Methadone is a diphenylpropylamine. It has very good oral bioavailability (~85%) with an oral to parenteral ratio of 1:2. Its plasma half-life can be highly variable (3–50h, average 24h) but its duration of action is relatively short. With repeated dosing, problems with accumulation can occur because of this discrepancy between half-life and analgesic effect. Careful monitoring is therefore required when converting patients to long-term methadone. A lso, there is incomplete cross-tolerance with morphine. The racemic mixture in common use has agonist actions at the MOP receptor (mainly the laevo isomer) as well as antagonist activity at the NMDA receptor dextro isomer). Given the importance of this receptor in central sensitisation in a variety of pain states, there may be cases where methadone offers particular advantages over and above other opioids (e.g. neuropathic pain). Plasma concentrations of methadone can be reduced by carbamazepine, and its metabolism is accelerated by phenytoin.

Safety Profile

Poison by ingestion, intraperitoneal, intravenous, subcutaneous, and intraduodenal routes. Human systemic effects: coma, nausea or vomiting, respiratory changes, respiratory depression, somnolence. An experimental teratogen. Experimental reproductive effects. Caution: Abuse leads to habituation or addiction. When heated to decomposition it emits toxic fumes of NOx. See also METHADONE HYDROCHLORIDE.

(+/-)-METHADONESupplier

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