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Guerra et al. J Transl Genet Genom 2022;6:304-21 https://dx.doi.org/10.20517/jtgg.2022.08 Page 308

Table 1. Pharmacogenetics of dopaminergic agonists in the treatment of neurogenic dysphagia

Drug Properties Pharmacogenetics
Name: Levodopa Pathogenic genes: ANKK1, BDNF, LRRK2, PARK2
IUPAC Name: l-Tyrosine-3-hydroxy Mechanistic genes: CCK, CCKAR, CCKBR, DRD1, DRD2, DRD3, DRD4, DRD5, GRIN2A,
Molecular Formula: C H NO GRIN2B, HCRT, HOMER1, LMO3, OPRM1
9 11 4
Molecular Weight: 197.19 g/mol Metabolic genes: Substrate: COMT, CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4,
Mechanism: Levodopa circulates in the plasma to the blood–brain barrier, CYP3A5, DBH, DDC, G6PD, MAOB, TH, UGT1A1, UGT1A9
where it crosses and is then converted by striatal enzymes to dopamine. Carbidopa inhibits the Transporter genes: SLC22A1, SLC6A3, SLC15A1 (inhibitor). SLC16A10 (inhibitor),
peripheral plasma breakdown of levodopa by inhibiting its carboxylation, and thereby increases SLC7A5, SLC7A8
available levodopa at the blood–brain barrier Pleiotropic genes: ACE, ACHE
Effect: Antiparkinsonian agents, dopamine precursors

Name: Cabergoline Pathogenic genes: BDNF, GSK3B
IUPAC Name: Ergoline-8β-carboxamide, N-[3-(dimethylamino)propyl]-N-[(ethylamino)carbonil]-6- Mechanistic genes: ADRA1A, ADRA1B,ADRA1D, ADRA2A, ADRA2B, ADRA2C, ADRB1,
(2-propenyl) ADRB2, AKT1, BDNF, CNR1, DRD1, DRD2, DRD3, DRD4, DRD5, GSK3B, HTR1A, HTR1B,
Molecular Formula: C H N O HTR1D, HTR2A, HTR2B, HTR2C, HTR7
26 37 5 2
Molecular Weight: 451.60 g/mol Metabolic genes: Substrate: COMT, CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4
Mechanism: A long-acting dopamine receptor agonist. (minor), CYP3A5, DDC
Has high binding affinity for dopamine D2-receptors and lesser affinity for D1, α1- and α2-adrenergic, Transporter genes: ABCB1
and serotonin (5-HT1 and 5-HT2) receptors.
Reduces serum prolactin concentrations by inhibiting release of prolactin from the anterior pituitary
gland (agonist activity at D2 receptors)
Effect: Antiparkinsonian agents, ergot-derivative dopamine receptor agonists
Name: Rotigotine Pathogenic genes: ANKK1, BDNF, LRRK2
Molecular Formula: C H NOs Mechanistic genes: CCK, CCKAR, CCKBR, DRD1, DRD2, DRD3, DRD4, DRD5, GRIN2A,
19 25
Molecular Weight: 315.47 g/mol GRIN2B, HCRT, HOMER1, LMO3, OPRM1, HTR1A, ADRA2B
Mechanism: A non-ergot dopamine receptor agonist with specificity for D3-, D2-, and D1-dopamine Metabolic genes:
receptors. Substrate: COMT, MAOB, CYP3A4, CYP2D6
Although the precise mechanism of action of Rotigotine is unknown, Inhibitor: CYP2D6, CYP2C19
it is believed to be due to stimulation of postsynaptic dopamine D2-type autoreceptors within Transporter genes: SLC22A1, SLC6A3
substantia nigra in brain, leading to improved dopaminergic transmission in motor areas in basal Pleiotropic genes: ACE, APOE
ganglia, notably caudate nucleus/putamen regions
Effect: Antiparkinsonian agents, non-ergot-derivative dopamine receptor agonists
Name: Apomorphine Pathogenic genes: PARK2
Molecular Formula: C H NO HCl H O Mechanistic genes: ADRA2A, ADRA2B, ADRA2C, CALY, DRD1, DRD2, DRD3, DRD4,
17 17 2 1/2 2
Molecular Weight: 312.79 g/mol DRD5, HTR1A, HTR1B, HTR1D, HTR2A, HTR2B, HTR2C
Mechanism: Stimulates postsynaptic D2-type receptors within the caudate-putamen in the brain Metabolic genes:
Effect: Antiparkinsonian agents, non-ergot-derivative dopamine receptor agonists Substrate: COMT, CYP1A2 (minor), CYP2B6, CYP2C9 (minor), CYP2C19 (minor),
CYP2D6, CYP3A4 (minor), CYP3A5, DDC, UGT1A1, UGT1A9, SULT1A1, SULT1A2,
SULT1A3, SULT1E1, SULT1B1
Inhibitor: CYP1A2 (weak), CYP2C19 (weak), CYP3A4 (weak)
Transporter genes: SLC18A2
Name: Amantadine Pathogenic genes: PARK2
IUPAC Name: Tricyclo[3.3.1.13,7]decan-1-amine, hydrochloride Mechanistic genes: CCR5, CXCR4, DRD1, DRD2, GRIN3A, CHRNA3, CHRNA4, CHRNA7
Molecular Formula: C H NHCl Metabolic genes:
10
17
Molecular Weight: 187.71 g/mol Substrate: COMT, CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5, DDC,
Mechanism: Antiparkinsonian activity may be due to inhibition of dopamine reuptake into presynaptic UGT1A1, UGT1A9