Methadone Hydrochloride: Structure,Synthesis,SAR,Mechanism,Uses

Methadone Hydrochloride

Structure –

Here is the chemical structure of Methadone Hydrochloride:

Methadone Hydrochloride

 

Methadone hydrochloride is a synthetic opioid that is primarily used to manage opioid addiction and chronic pain.

Synthesis –

Methadone hydrochloride can be synthesized in a multistep process starting from 4-cyano-2-dimethylamino-4,4-diphenylbutane. Here is a simplified outline of the synthesis:

  1. Condensation: 4-cyano-2-dimethylamino-4,4-diphenylbutane is condensed with acetic anhydride to form 4-cyano-2-dimethylamino-4,4-diphenylbutyric acid.
  2. Reduction: The cyano group in the butyric acid derivative is reduced to a ketone using lithium aluminum hydride.
  3. Cyclization: The ketone is then cyclized using hydrochloric acid to form racemic methadone.
  4. Resolution: The racemic methadone is resolved into its enantiomers using a chiral acid, typically (+)-tartaric acid.
  5. Salt formation: The enantiomer of interest is then converted into its hydrochloride salt by reacting with hydrochloric acid.

Overall, the synthesis of methadone hydrochloride is a complex process that requires specialized knowledge and equipment. It should only be performed by trained professionals in a controlled laboratory setting.

 

OR

I apologize for the confusion earlier. Here is a more detailed explanation of the synthesis of Methadone Hydrochloride with the corresponding structure:

  1. The starting material for the synthesis is 4-dimethylamino-2,2-diphenylvalerophenone.

Methadone Hydrochloride

  1. The first step involves reacting 4-dimethylamino-2,2-diphenylvalerophenone with methyl iodide and potassium carbonate to form 4-dimethylamino-2,2-diphenyl-3-methylbutyronitrile.

Methadone Hydrochloride

  1. The nitrile group is then reduced using lithium aluminum hydride to form 4-dimethylamino-2,2-diphenyl-3-methylbutanol.

Methadone Hydrochloride

  1. The next step involves reacting the alcohol with thionyl chloride to form 4-dimethylamino-2,2-diphenyl-3-methylbutyl chloride.
Methadone Hydrochloride
  1. The final step involves reacting 4-dimethylamino-2,2-diphenyl-3-methylbutyl chloride with racemic α-methylbenzylamine to form Methadone.
Methadone Hydrochloride
  1. Finally, Methadone is converted to Methadone Hydrochloride by reacting it with hydrochloric acid.
Methadone Hydrochloride

SAR –

The SAR (Structure-Activity Relationship) of Methadone Hydrochloride is as follows:

Methadone Hydrochloride is a synthetic opioid that acts as a full agonist at the mu-opioid receptor. It is structurally similar to other opioids, such as morphine and fentanyl, but it has some unique properties that make it useful in the treatment of opioid dependence.

The basic structure of Methadone Hydrochloride is a phenylpiperidine moiety, which is the core structure of many opioid analgesics. The substitution of the phenyl ring with a 4,4-dimethyl-3-hydroxyphenyl group in Methadone Hydrochloride results in increased lipophilicity and decreased potency compared to morphine.

The presence of a tertiary amine group in Methadone Hydrochloride allows it to undergo ionization and form a salt with hydrochloric acid, which enhances its water solubility and facilitates its administration as an injectable or oral solution.

The N-methyl group in Methadone Hydrochloride contributes to its high oral bioavailability and prolonged duration of action, as it slows down its metabolism and elimination by the liver.

The SAR of Methadone Hydrochloride suggests that its pharmacological properties are determined by its structural features, including its lipophilicity, potency, water solubility, oral bioavailability, and metabolism. These properties make it a useful medication for opioid dependence, as it can reduce withdrawal symptoms and cravings without causing the euphoric effects and respiratory depression associated with other opioids.

Mechanism –

Methadone hydrochloride is a synthetic opioid that acts as a full agonist at the mu-opioid receptor. Its mechanism of action is similar to that of other opioids such as morphine, fentanyl, and heroin.

Methadone hydrochloride binds to mu-opioid receptors located in the central nervous system, peripheral tissues, and organs. This binding leads to a decrease in the transmission of pain signals and an increase in the release of dopamine, a neurotransmitter that produces feelings of pleasure and well-being.

Methadone hydrochloride also blocks the reuptake of norepinephrine and serotonin, two other neurotransmitters that play a role in pain perception and mood regulation.

The binding of Methadone hydrochloride to the mu-opioid receptor results in the opening of potassium channels, which leads to hyperpolarization of the cell membrane and a decrease in the firing rate of neurons. This decrease in neuronal activity results in decreased pain perception and a sense of relaxation.

Methadone hydrochloride has a long half-life, which means it stays in the body for a longer period than other opioids. This property makes it useful in the treatment of opioid dependence as it can reduce withdrawal symptoms and cravings without causing the euphoric effects and respiratory depression associated with other opioids.

In summary, the mechanism of action of Methadone hydrochloride involves binding to mu-opioid receptors, blocking the reuptake of norepinephrine and serotonin, and opening of potassium channels, resulting in decreased pain perception, increased dopamine release, and decreased neuronal activity.

Uses –

it is primarily used for the treatment of opioid dependence and chronic pain management.

In the treatment of opioid dependence, it is used as a long-acting opioid agonist to reduce withdrawal symptoms and cravings. It can be used as part of a comprehensive treatment plan that includes counseling, behavioral therapy, and other support services to help individuals overcome their addiction to opioids.

In chronic pain management, it may be used when other pain medications have not provided adequate relief or when there is a risk of addiction or misuse of other opioids. Methadone hydrochloride’s long duration of action and ability to provide sustained pain relief make it a useful option for some patients with chronic pain.

Additionally, it is sometimes used off-label for the treatment of other conditions such as restless leg syndrome and neuropathic pain.

It is important to note that it is a controlled substance with a high potential for abuse and addiction, and it should only be used under the close supervision of a healthcare professional.

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