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Page 307 Guerra et al. J Transl Genet Genom 2022;6:304-21 https://dx.doi.org/10.20517/jtgg.2022.08

physical signs were evaluated, is also observed with other dopamine agonists such as cabergoline and
amantadine; the elderly population, in particular, may benefit from treatment with dopamine agonists [30,31] .

The search for new compounds to treat ND also includes natural supplements that contain dopamine, for
use mainly in groups where dosage or side effects may be contraindicated, such as children or the elderly.
Natural sources of dopamine include Mucuna pruriens, Vicia faba, or Musa cavendishii [32-34] . In fact, several
studies in patients with Parkinson’s disease reveal the effectiveness of these treatments with extracts derived
from these products; these compounds reduce the risk of adverse effects such as dyskinesias as well as
induce epigenetic and pharmacoepigenetic modifications [35,36] .

Pharmacogenetics of dopaminergic agonists in the treatment of neurogenic dysphagia
[37]
Anti-ND drugs exhibit different specific pharmacogenetic profiles [Table 1] . All of the medications used
to treat ND show, among others, DRD1 as a mechanistic gene and the binding of drugs to this receptor. All
of the anti-ND drugs have COMT as substrates, where COMT shortens the activity of these dopaminergic
[38]
drugs . Moreover, the COMT rs4680 polymorphism may induce motor complications such as dyskinesia
during treatment with levodopa [38-40] . Levodopa also has DBH as substrate . ADORA2A SNPs and
[37]
HOMER1 variants are associated with L-DOPA-induced adverse motor (e.g., dyskinesia) and psychotic
symptoms [41,42] . A haplotype integrating -141CIns/Del, rs2283265, rs1076560, C957T, TaqIA, and rs2734849
polymorphisms at the DRD2/ANKK1 gene region is linked to L-DOPA-induced motor dysfunction .
[43]
SLC6A3 is a genetic modifier of the treatment response to L-DOPA . The multi-drug resistance gene
[44]
[45]
(MDR1) C1236T polymorphism may also influence pharmacotherapy and SNPs in genes that encode the
dopamine transporter (DAT; SLC6A3) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2) .
[46]
Despite the fact that dopamine agonist therapy has applicability in other ND diseases, these studies focus on
Parkinson’s disease, which limits inferences in other acquired or degenerative neurological illnesses.

Antidopaminergics and neurogenic dysphagia
In a significant number of cases, the causes of ND can be induced or exacerbated by certain drugs [9-11] . Many
patients with different neurological conditions are treated with antidopaminergic medication [10,11] . Adverse
reactions are especially frequent in senescence and are relevant since they are reversible, and dysphagia may
be the only or the predominant extrapyramidal symptom. Although it is recommended that drug intake be
minimized as much as possible, this is not feasible in many cases. It is therefore recommended that the drug
dose be adjusted to avoid the aforementioned side effects. Knowing the pharmacogenetic profiles of these
[37]
drugs is, therefore, very important to therapeutic strategies [Table 2].

Antipsychotics, as antidopaminergic medications, are primarily metabolized through
CYP1A2/2D6/3A4/2C19 . Of these, CYP2D6 is the most relevant because 40% of these neuroleptics are
[47]
major substrates of this enzyme. CYP2D6, however, is associated with side effects. Other genes such as
HTR2A, SLC18A2, GRIK3, and DRD2 are linked to extrapyramidal reactions . Drugs that exert an
[48]
antidopaminergic effect on DRD1 are of particular interest. In ND, DRD1 is the pathogenic gene that is
involved in the pharmacogenomic response to haloperidol, aripiprazole, olanzapine, quetiapine, or
risperdone. Other DRDs (not DRD1) pathogenic variants mediate the adverse effects of antipsychotic drugs
such as sulpiride, domperidone, and metroclopramide, causing oropharyngeal dysphagia; this suggests that
[37]
other dopamine- and non-dopamine pathways mediate blocking of the swallowing phase .

TRANSIENT RECEPTOR POTENTIAL CHANNEL (TRP) GENES
Transient receptor potential (TRP) channel genes encode ion channels that are classified into two broad
groups: (i) Group 1 includes TRPC (canonical), TRPV (vanilloid), TRPVL (vanilloid-like), TRPM