Active ingredient: Levodopa - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Dopamine Agents
• Antiparkinson Agents
• Antidyskinetics

Dosage Forms

• Tablet (pink, scored, each containing levodopa 0.1 g)

Brands / Synonyms

Atamet; Bendopa; Brocadopa; Carbidopa and Levodopa; Cidandopa; DA; Deadopa; DOPA; Dopaflex; Dopaidan; Dopal; Dopal-Fher; Dopalina; Dopar; Doparkine; Doparl; Dopasol; Dopaston; Dopastral; Doprin; Eldopal; Eldopar; Eldopatec; Eurodopa; Helfo-Dopa; Insulamina; L-Dihydroxyphenylalanine; L-DOPA; Laradopa; Larodopa; Ledopa; Levedopa; Levopa; Maipedopa; Parcopa; Parda; Pardopa; Prodopa; Sinemet; Sinemet CR; Stalevo; Syndopa; Veldopa; Weldopa

Indications

For the treatment of idiopathic Parkinson's disease (Paralysis Agitans), postencephalitic parkinsonism, symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication, and manganese intoxication.

Pharmacology

Levodopa (L-dopa) is used to replace dopamine lost in Parkinson's disease because dopamine itself cannot cross the blood-brain barrier where its precursor can. However, L-DOPA is converted to dopamine in the periphery as well as in the CNS, so it is administered with a peripheral DDC (dopamine decarboxylase) inhibitor such as carbidopa, without which 90% is metabolised in the gut wall, and with a COMT inhibitor if possible; this prevents about a 5% loss. The form given therapeutically is therefore a prodrug which avoids decarboxylation in the stomach and periphery, can cross the blood-brain barrier, and once in the brain is converted to the neurotransmitter dopamine by the enzyme aromatic-L-amino-acid decarboxylase.

Mechanism of Action

Striatal dopamine levels in symptomatic Parkinson's disease are decreased by 60 to 80%, striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine.

Absorption

Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system.

Toxicity

Oral, mouse: LD₅₀ = 2363 mg/kg; Oral, rabbit: LD₅₀ = 609 mg/kg; Oral, rat: LD₅₀ = 1780 mg/kg.

Biotrnasformation / Drug Metabolism

95% of an administered oral dose of levodopa is pre-systemically decarboxylated to dopamine by the L-aromatic amino acid decarboxylase (AAAD) enzyme in the stomach, lumen of the intestine, kidney, and liver. Levodopa also may be methoxylated by the hepatic catechol-O-methyltransferase (COMT) enzyme system to 3-O-methyldopa (3-OMD), which cannot be converted to central dopamine.

Contraindications

Monoamine oxidase (MAO) inhibitors and Larodopa should not be given concomitantly and these inhibitors must be discontinued 2 weeks prior to initiating therapy with Larodopa. Larodopa is contraindicated in patients with known hypersensitivity to the drug and in narrow angle glaucoma.

Because levodopa may activate a malignant melanoma, it should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.

Drug Interactions

No information provided.