Anti-Parkinson's Disease Drugs and Pharmacogenetic Considerations

Expert Opin Drug Metab Toxicol. 2013 Jul;9(7):859-74. doi: 10.1517/17425255.2013.789018. Epub 2013 Apr 9.

Abstract

Introduction: The development of pharmacogenetic-based clinical practice guidelines for the use of anti-Parkinson's disease drugs requires, as a pre-requisite, the identification and validation of genetic biomarkers. These biomarkers are then used as surrogate endpoints. This review analyzes potential genetic biomarkers which can be used to improve anti-Parkinson's disease therapy.

Areas covered: The authors present an overview of current knowledge of pharmacogenetic implications of anti-Parkinson's disease drugs, including genes coding for the corresponding drug-metabolizing enzymes and drug targets. The gene/drug pairings with the strongest potential for pharmacogenetic recommendations include: CYP2C19/benztropine, COMT/levodopa and entacapone, CYP2B6/selegiline, UGT1A/entacapone, DRD2/ropinirole, pramipexole and cabergoline, and DRD3/ropinirole and pramipexole. Evidence supporting the effect of substrates, inhibitor or inducers for drug specific metabolizing enzymes in anti-Parkinson's disease drug response includes CYP1A2 in the response to ropinirole and rasagiline, and CYP3A4 in the response to bromocriptine, lisuride, pergolide and cabergoline. The authors present and discuss the current information on gene variations according to the 1000 genomes catalog and other databases with regards to anti-Parkinson's disease drugs. They also review and discuss the clinical implications of these variations.

Expert opinion: The goal of pharmacogenomic testing for anti-Parkinson's disease drugs should be conservative and aimed at selecting determined drugs for determined patients. However, much additional research is still needed to obtain reliable pre-prescription tests.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Benzothiazoles / therapeutic use
  • Benztropine / therapeutic use
  • Bromocriptine / therapeutic use
  • Cabergoline
  • Catechols / therapeutic use
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Ergolines / therapeutic use
  • Genetic Markers
  • Humans
  • Indans / therapeutic use
  • Indoles / therapeutic use
  • Levodopa / therapeutic use
  • Lisuride / therapeutic use
  • Nitriles / therapeutic use
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics*
  • Pergolide / therapeutic use
  • Pharmacogenetics*
  • Pramipexole
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / genetics
  • Receptors, Dopamine D3 / metabolism
  • Reproducibility of Results
  • Selegiline / therapeutic use

Substances

  • Benzothiazoles
  • Catechols
  • Cytochrome P-450 CYP1A2 Inhibitors
  • DRD2 protein, human
  • DRD3 protein, human
  • Ergolines
  • Genetic Markers
  • Indans
  • Indoles
  • Nitriles
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • rasagiline
  • ropinirole
  • Benztropine
  • Pergolide
  • Selegiline
  • Bromocriptine
  • Levodopa
  • entacapone
  • Pramipexole
  • Lisuride
  • Aryl Hydrocarbon Hydroxylases
  • CYP1A2 protein, human
  • CYP2B6 protein, human
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Cabergoline