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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 310



                          Table 2. Pharmacogenetics of antidopaminergic drugs and the risk of neurogenic dysphagia

                          Drug                  Properties                                                                                        Pharmacogenetics
                                                Name: Haloperidol                                                                                 Pathogenic genes: ADRA1A, ADRA2A, ADRA2B, ADRA2C, BDNF, DRD1, DRD2,
                                                IUPAC Name: 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one          DRD3, DRD4, DTNBP1, GRIN2B, HTR2A
                                                Molecular Formula: C H ClFNO                                                                      Mechanistic genes: ANKK1, BDNF, COMT, DRD1, DRD2, DRD3, DTNBP1,
                                                                   21  23    2
                                                Molecular Weight: 375.864223 g/mol                                                                GRIN2A, GRIN3B, GRIN2C, GRIN2B, SLC6A3, MCHR1, SLC18A2, HTR2C,
                                                Mechanism: Haloperidol is a butyrophenone antipsychotic which blocks postsynaptic mesolimbic      SIGMAR1, HRH1, CHRM3, HTR1A, HTR6, HTR7
                                                dopaminergic D1 and D2 receptors in brain. Depresses release of hypothalamic and hypophyseal hormones.   Metabolic genes:
                                                Believed to depress reticular activating system                                                   Substrate: CBR1, CYP1A1 (minor), CYP1A2 (minor), CYP2A6, CYP2C8 (minor),
                                                Effect: Antipsychotic agent, Serotonergic antagonist, Dopaminergic antagonist, antiemetic, antidyskinesia   CYP2C9 (minor), CYP2C19 (minor), CYP2D6 (major), CYP3A4/5 (major),
                                                agent, sedative effects, hypotension                                                              CYP3A7, GSTP1, UGT1A9
                                                                                                                                                  Inhibitor: CYP2D6 (moderate), CYP3A4 (moderate)
                                                                                                                                                  Transporter genes: ABCB1 (substrate/inhibitor), ABCC1, KCNE1, KCNE2,
                                                                                                                                                  KCNH2, KCNJ11, KCNQ1, SLC6A3
                                                                                                                                                  Pleiotropic genes: CHRM2, FOS, GSK3B, HRH1, HTR2A, HTT, IL1RN

                                                Name: Sulpiride.                                                                                  Pathogenic genes: DRD2, DRD3, DRD4
                                                IUPAC Name: N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide                     Mechanistic genes: DRD2, DRD3, DRD4, PRLH, CA2, CA3
                                                Molecular Formula: C H N O S                                                                      Metabolic genes:
                                                                   15  23  3  4
                                                Molecular Weight: 341.42582 g/mol                                                                 Substrate: CYP1A2, CYP2B1, CYP3As
                                                Mechanism: It is a selective antagonist at postsynaptic D2 and D3 receptors. It appears to lack effects on   Inhibitor: BCHE, CYP1A2, CYP2B1, CYP3As
                                                norepinephrine, acetylcholine, serotonin, histamine, or GABA receptors. It also stimulates secretion of   Transporter genes: SLC22A1, SLC22A2, SLC47A1, SLC47A2, SLC22A3, ABCB1,
                                                prolactin.                                                                                        ABCG2
                                                Effect: Antipsychotic agent, dopaminergic antagonist, antidepressant effect, antiemesis, sedation
                                                (> 600 mg/day), dopamine reuptake inhibition (< 200 mg/day), antiemesis, antimigraine effects,
                                                antivertiginous activity, prolactin-releasing stimulation
                                                Name: Aripiprazole.                                                                               Pathogenic genes: DRD1, DRD2, DRD3, DRD4, HTR1A, HTR2A, HTR2C
                                                IUPAC Name: 7-{4-[4-(2,3-dichlorophenyl) piperazin-1-yl]butoxy}-1,2,3,4-tetrahydroquinolin-2-one   Mechanistic genes: ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, CHRM1,
                                                Molecular Formula: 448.38538 g/mol                                                                CHRM2, CHRM3, CHRM4, CHRM5, CALy, GSTP1,DRD1, DRD2, DRD3, DRD4,
                                                Molecular Weight: C H Cl N O                                                                      HRHs, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR3A, HTR6,
                                                                  23  27  2  3  2
                                                Mechanism: Partial agonist at the D2 and 5-HT1A receptors, and as an antagonist at the 5-HT2A receptor   HTR7, CYP1A1
                                                Effect: Antipsychotic agent, H1-receptor antagonist, serotonergic agonist                         Metabolic genes:
                                                                                                                                                  Substrate: CYP1A2, CYP2A6, CYP2D6 (major), CYP3A4 (major), CYP2C8,
                                                                                                                                                  CYP2C9, CYP2C19, CYP3A5, FMO3, UGT1A4
                                                                                                                                                  Inhibitor: CYP2D6, CYP3A4, CYP2C19
                                                                                                                                                  Transporter genes: ABCB1
                                                Name: Olanzapine.                                                                                 Pathogenic genes: COMT, DRD1, DRD2, DRD3, DRD4, GRM3, HTR2A, HTR2C,
                                                                                                                          3 7
                                                IUPAC Name: 5-methyl-8-(4-methylpiperazin-1-yl)-4-thia-2,9-diazatricyclo[8.4.0.0 , ]tetradeca-    LPL
                                                1(14),3(7),5,8,10,12-hexaene                                                                      Mechanistic genes: ABCB1, ADRA1A, ADRA1B, ADRB3, AHR, BDNF, CHRM1,
                                                Molecular Formula: C H N S                                                                        CHRM2, CHRM3, CHRM4, CHRM5, COMT, DRD1, DRD2, DRD3, DRD4, DRD5,
                                                                   17  20  4
                                                Molecular Weight: 312.4325 g/mol                                                                  GABRs, GRIN2B, HRH1, HTR2A, HTR2C, HTR3A, HTR6, HRH1,LEP, RGS2, RGS7,
                                                Mechanism: It displays potent antagonism of serotonin 5-HT2A and 5-HT2C, dopamine D1-4, histamine H1   SLC6A4, STAT3, TMEM163
                                                and α1-adrenergic receptors, moderate antagonism of 5-HT3 and muscarinic M1-5 receptors, and weak   Metabolic genes:
                                                binding to GABA-A, BZD, and β-adrenergic receptors.                                               Substrate: COMT, CYP1A2 (major), CYP2C9, CYP2D6 (major), CYP3A4,
                                                Effect: Antipsychotic agent, GABA modulator, muscarinic antagonist, serotonin uptake inhibitor, dopaminergic   CYP3A5, FMO1, FMO3, GSTM3, TPMT, UGT1A1, UGT1A4, UGT2B10
                                                antagonist, serotonergic antagonist, histamine antagonist, antiemetic activity                    Inhibitor: CYP1A2 (weak), CYP2C9 (weak), CYP2C19 (weak), CYP2D6 (weak),
                                                                                                                                                  CYP3A4 (weak)
                                                                                                                                                  Inducer: GSTM1, MAOB, SLCO3A1
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