• Bridging Genetic Variations from Pharmacogenomics to Improving Medications Efficiency in More Precise Parkinson's Disease Therapy
  • Maryam Mohsenian,1,* Alireza Nouri,2
    1. Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    2. Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


  • Introduction: Parkinson's disease (PD) is a Neurodegenerative disorder, which characterized by a reduction of dopaminergic cells in the brain, located substantia nigra. Dopamine receptor agonists (DRAs) are a class of medications commonly prescribed for the management of PD symptoms. However, the response of DRAs can vary significantly among patients, and individual genetic factors play a crucial role in determining treatment outcomes. The pharmacogenomic considerations when prescribing DRAs for Parkinson's disease highlight the potential of personalized medicine in optimizing treatment outcomes and minimizing unwanted effects. By identifying genetic variations associated with DRA induction, personalized medicine approaches could be implemented in choosing better medications and dosage adjustments for individuals. Variations in critical genes that play a part in dopamine metabolism, such as receptor signaling and drug biotransformation, have been identified as potential precursors of DRAs in Parkinson's disease.
  • Methods: This comprehensive review aims to identify a holistic focus on gene-drug interactions, which result in diverse responses to one drug in different patients. Relevant databases, including Genecard, Scopus, and Web of Science, were searched by using keywords such as "pharmacogenomics," "dopamine receptor agonists," "Parkinson's disease," and "treatment." Relevant articles published between 2018 and 2023 were included in the study.
  • Results: Several studies have scoped on single nucleotide polymorphisms (SNPs) in genes such as DRD2, DRD3, and COMT, which have been associated with variations in DRA efficacy and tolerability. The DRD2 gene encodes dopamine D2 receptors, and SNPs in this gene have been associated with differences in DRA response. For instance, the TAQ1, a polymorphism (rs1800497) in the DRD2 gene, has been linked to a decrease in the D2 receptor expression in the striatum. Depending on allele expression, they have been linked to variations in essential cognitive control functions. Similarly, SNPs in the DRD3 gene, which encodes dopamine D3 receptors, have also been implicated in DRA response. The Ser9Gly polymorphism (rs6280) in the DRD3 gene has been associated with a different response to DRAs such as Pramipexole. Additionally, Pramipexole must be administered at greater doses to PD patients with the Gly/Gly genotype to be clinically efficient compared to those with the Ser allele. The COMT gene encodes catechol-O-methyltransferase, an enzyme involved in dopamine metabolism. Variations in this gene, particularly the Val158Met polymorphism (rs4680), have been associated with differences in drug response. The rs4608 COMT gene polymorphism changes the motor response to entacapone, a COMT inhibitor. Individuals with higher COMT enzyme activity respond greater than those with lower COMT enzyme activity.
  • Conclusion: Pharmacogenetics considerations become crucial when optimizing the use of dopamine receptor agonists for Parkinson's disease; by incorporating pharmacogenetic information into care decisions, personalized therapy approaches can refine treatment outcomes. Nevertheless, several challenges must be addressed before pharmacogenetics can be fully embedded into clinical practice. Standardized testing protocols and guidelines for genetic testing are essential tools to ensure scalable and reliable results. Moreover, the viability of pharmacogenetic testing and the availability of alternative treatment options must be accounted for to ensure equitable access for all patients. Further research and clinical trials are needed to validate these findings and translate them into routine clinical practice. With continued advancements in pharmacogenetics, the future of personalized medicine for Parkinson's disease looks more promising.
  • Keywords: parkinson's disease, dopamine receptor agonists, pharmacogenomics, personalized medicine