Mechanism of action of dopaminergic agents in Parkinson's disease.
Article Details
- CitationCopy to clipboard
Koller WC, Rueda MG
Mechanism of action of dopaminergic agents in Parkinson's disease.
Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8. doi: 10.1212/wnl.50.6_suppl_6.s11.
- PubMed ID
- 9633680 [ View in PubMed]
- Abstract
As the substantia nigra degenerates in Parkinson's disease (PD), the nigrostriatal pathway is disrupted, reducing striatal dopamine and producing PD symptoms. Although dopamine does not readily cross the blood-brain barrier, its precursor, levodopa, does. Levodopa is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O-methyltransferase (COMT). Because gastric AADC and COMT degrade levodopa, the drug is given with inhibitors of AADC (carbidopa or benserazide), and inhibitors of COMT will also enter clinical use. Although the exact site of decarboxylation of exogenous levodopa to dopamine in the brain is unknown, most striatal AADC is located in nigrostriatal dopaminergic nerve terminals. Newly synthesized dopamine is stored in the terminals and then released, stimulating postsynaptic dopamine receptors and mediating the antiparkinsonian action of levodopa. Dopamine agonists act directly on postsynaptic dopamine receptors, thus obviating the need for metabolic conversion, storage, and release. How the actions of dopaminergic drugs produce side effects and how these side effects should be managed are discussed.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Levodopa Dopamine D1 receptor Protein Humans YesAgonistDetails Levodopa Dopamine D2 receptor Protein Humans YesAgonistDetails Levodopa Dopamine D3 receptor Protein Humans YesAgonistDetails Levodopa Dopamine D4 receptor Protein Humans YesAgonistDetails Levodopa Dopamine D5 receptor Protein Humans YesAgonistDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAmantadineMetoclopramide The therapeutic efficacy of Amantadine can be decreased when used in combination with Metoclopramide. AmantadineFlupentixol The therapeutic efficacy of Amantadine can be decreased when used in combination with Flupentixol. ApomorphineFlupentixol The therapeutic efficacy of Apomorphine can be decreased when used in combination with Flupentixol. BenserazideMetoclopramide The therapeutic efficacy of Benserazide can be decreased when used in combination with Metoclopramide. BenserazideFlupentixol The therapeutic efficacy of Benserazide can be decreased when used in combination with Flupentixol.