indication

For the treatment and management of opiate dependence. It is sometimes used to treat severe pain in terminal patients.

pharmacology

Levomethadyl acetate (also known as LAAM) is a synthetic synthetic opioid analgesic with multiple actions quantitatively similar to those as morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, levomethadyl acetate is more active and more toxic than morphine. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. In this respect, the drug is similar to Methadone and also has structural similarities to it. The levomethadyl acetate abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.

mechanism of action

Opiate receptors (Mu, Kappa, Delta) are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Levomethadyl acetate effectively opens calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist), resulting in hyperpolarization and reduced neuronal excitability.

toxicity

Signs of overdose include apnea, circulatory collapse, pulmonary edema, cardiac arrest, and death.

biotransformation

Levomethadyl acetate undergoes extensive first-pass metabolism to the active demethylated metabolite nor-levomethadyl acetate, which is further demethylated to a second active metabolite, dinor-levomethadyl acetate. These metabolites are more potent than the parent drug.

absorption

Levomethadyl acetate is rapidly absorbed from an oral solution.

half life

2.6 days

drug interactions

Itraconazole: Itraconazole increases the effect/toxicity of levomethadyl

Quinupristin: This combination presents an increased risk of toxicity