DT-Web

DB00714 - Apomorphine


Identification
Name Apomorphine
Accession Number DB00714 (APRD00531)
Type small molecule
Description A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 267.3224
Groups approved
Monoisotopic Weight 267.125928793
Pharmacology
Indication For the acute, intermittent treatment of hypomobility, off episodes (end-of-dose wearing off and unpredictable on/off episodes) associated with advanced Parkinson's disease.
Mechanism of action The precise mechanism of action of apomorphine as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the brain. Apomorphine has been shown to improve motor function in an animal model of Parkinson's disease. In particular, apomorphine attenuates the motor deficits induced by lesions in the ascending nigrostriatal dopaminergic pathway with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in primates.
Absorption 100% following subcutaneous administration
Protein binding ~50%-albumin
Biotransformation Hepatic
Route of elimination Not Available
Toxicity LD50=0.6 mmoles/kg (mice, intraperitoneal)
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Entacapone Entacapone increases the effect and toxicity of the sympathomimetic, apomorphine.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Paliperidone The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, apomorphine. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Thiothixene may also antagonize the effects of the anti-Parkinsonian agent, Apomorphine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or doses changed.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). Antagonism may also occur between zuclopenthixol, a dopamine D2 receptor antagonist, and apomorphine, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.
Food Interactions Not Available

Targets


D(3) dopamine receptor
Name D(3) dopamine receptor
Gene Name DRD3
Pharmacological action yes
Actions agonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.5882
D(4) dopamine receptor
Name D(4) dopamine receptor
Gene Name DRD4
Pharmacological action yes
Actions agonist
References
  • Boeckler F, Russig H, Zhang W, Lober S, Schetz J, Hubner H, Ferger B, Gmeiner P, Feldon J: FAUC 213, a highly selective dopamine D4 receptor full antagonist, exhibits atypical antipsychotic properties in behavioural and neurochemical models of schizophrenia. Psychopharmacology (Berl). 2004 Aug;175(1):7-17. Epub 2004 Mar 6. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
  • Mansbach RS, Brooks EW, Sanner MA, Zorn SH: Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition. Psychopharmacology (Berl). 1998 Jan;135(2):194-200. - Pubmed
  • Melis MR, Succu S, Sanna F, Melis T, Mascia MS, Enguehard-Gueiffier C, Hubner H, Gmeiner P, Gueiffier A, Argiolas A: PIP3EA and PD-168077, two selective dopamine D4 receptor agonists, induce penile erection in male rats: site and mechanism of action in the brain. Eur J Neurosci. 2006 Oct;24(7):2021-30. - Pubmed
  • Sanner MA, Chappie TA, Dunaiskis AR, Fliri AF, Desai KA, Zorn SH, Jackson ER, Johnson CG, Morrone JM, Seymour PA, Majchrzak MJ, Faraci WS, Collins JL, Duignan DB, Prete Di CC, Lee JS, Trozzi A: Synthesis, SAR and pharmacology of CP-293,019: a potent, selective dopamine D4 receptor antagonist. Bioorg Med Chem Lett. 1998 Apr 7;8(7):725-30. - Pubmed
  • Succu S, Sanna F, Melis T, Boi A, Argiolas A, Melis MR: Stimulation of dopamine receptors in the paraventricular nucleus of the hypothalamus of male rats induces penile erection and increases extra-cellular dopamine in the nucleus accumbens: Involvement of central oxytocin. Neuropharmacology. 2007 Mar;52(3):1034-43. Epub 2006 Dec 11. - Pubmed
DTHybrid score 0.5515
D(2) dopamine receptor
Name D(2) dopamine receptor
Gene Name DRD2
Pharmacological action yes
Actions agonist
References
  • Yamada S, Harano M, Annoh N, Nakamura K, Tanaka M: Involvement of serotonin 2A rec -
  • Berlin I, de Brettes B, Aymard G, Diquet B, Arnulf I, Puech AJ: Dopaminergic drug response and the genotype (Taq IA polymorphism) of the dopamine D2 receptor. Int J Neuropsychopharmacol. 2000 Mar;3(1):35-43. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Kim HJ, Koh PO, Kang SS, Paik WY, Choi WS: The localization of dopamine D2 receptor mRNA in the human placenta and the anti-angiogenic effect of apomorphine in the chorioallantoic membrane. Life Sci. 2001 Jan 19;68(9):1031-40. - Pubmed
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
  • Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. - Pubmed
  • Lucht MJ, Kuehn KU, Schroeder W, Armbruster J, Abraham G, Schattenberg A, Gaensicke M, Barnow S, Tretzel H, Herrmann FH, Freyberger HJ: Influence of the dopamine D2 receptor (DRD2) exon 8 genotype on efficacy of tiapride and clinical outcome of alcohol withdrawal. Pharmacogenetics. 2001 Nov;11(8):647-53. - Pubmed
  • Yamada S: [Disruption of prepulse inhibition of acoustic startle as an animal model for schizophrenia] Nihon Shinkei Seishin Yakurigaku Zasshi. 2000 Oct;20(4):131-9. - Pubmed
  • Yamada S, Harano M, Annoh N, Nakamura K, Tanaka M: Involvement of serotonin 2A receptors in phencyclidine-induced disruption of prepulse inhibition of the acoustic startle in rats. Biol Psychiatry. 1999 Sep 15;46(6):832-8. - Pubmed
DTHybrid score 0.9148
Alpha-2C adrenergic receptor
Name Alpha-2C adrenergic receptor
Gene Name ADRA2C
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.6325
Alpha-2B adrenergic receptor
Name Alpha-2B adrenergic receptor
Gene Name ADRA2B
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.6457
5-hydroxytryptamine 2C receptor
Name 5-hydroxytryptamine 2C receptor
Gene Name HTR2C
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.6289
D(1B) dopamine receptor
Name D(1B) dopamine receptor
Gene Name DRD5
Pharmacological action unknown
Actions agonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.5158
5-hydroxytryptamine 1A receptor
Name 5-hydroxytryptamine 1A receptor
Gene Name HTR1A
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.7143
5-hydroxytryptamine 2A receptor
Name 5-hydroxytryptamine 2A receptor
Gene Name HTR2A
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.7878
5-hydroxytryptamine 2B receptor
Name 5-hydroxytryptamine 2B receptor
Gene Name HTR2B
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.489
Alpha-2A adrenergic receptor
Name Alpha-2A adrenergic receptor
Gene Name ADRA2A
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.8066
D(1A) dopamine receptor
Name D(1A) dopamine receptor
Gene Name DRD1
Pharmacological action unknown
Actions agonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Guo H, Tang Z, Yu Y, Xu L, Jin G, Zhou J: Apomorphine induces trophic factors that support fetal rat mesencephalic dopaminergic neurons in cultures. Eur J Neurosci. 2002 Nov;16(10):1861-70. - Pubmed
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
  • Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. - Pubmed
DTHybrid score 0.7826
5-hydroxytryptamine 1D receptor
Name 5-hydroxytryptamine 1D receptor
Gene Name HTR1D
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.5865
5-hydroxytryptamine 1B receptor
Name 5-hydroxytryptamine 1B receptor
Gene Name HTR1B
Pharmacological action unknown
Actions agonist
References
  • Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. - Pubmed
DTHybrid score 0.5937
D1 dopamine receptor-interacting protein calcyon
Name D1 dopamine receptor-interacting protein calcyon
Gene Name CALY
Pharmacological action unknown
Actions agonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.1746

Predictions


Id Partner name Gene Name Score
556 Alpha-1A adrenergic receptor ADRA1A 0.4439
4119 Cytochrome P450 2D6 CYP2D6 0.427
4512 Cytochrome P450 3A4 CYP3A4 0.3479
4200 Cytochrome P450 1A2 CYP1A2 0.3225
632 Alpha-1B adrenergic receptor ADRA1B 0.305
716 5-hydroxytryptamine 7 receptor HTR7 0.2805
492 Histamine H1 receptor HRH1 0.2155
1588 Multidrug resistance protein 1 ABCB1 0.2004
103 Muscarinic acetylcholine receptor M1 CHRM1 0.1747
789 Alpha-1D adrenergic receptor ADRA1D 0.1741
1256 5-hydroxytryptamine 6 receptor HTR6 0.1513
824 Sodium-dependent serotonin transporter SLC6A4 0.1464
274 Muscarinic acetylcholine receptor M5 CHRM5 0.1405
617 Muscarinic acetylcholine receptor M2 CHRM2 0.138
450 Muscarinic acetylcholine receptor M4 CHRM4 0.1366
3941 Amine oxidase [flavin-containing] A MAOA 0.1324
51 Muscarinic acetylcholine receptor M3 CHRM3 0.1308
511 5-hydroxytryptamine 1F receptor HTR1F 0.1284
528 5-hydroxytryptamine 1E receptor HTR1E 0.1184
4118 Cytochrome P450 3A5 CYP3A5 0.1084
540 Sodium-dependent noradrenaline transporter SLC6A2 0.1075
6016 Cytochrome P450 2C19 CYP2C19 0.1072
6145 Solute carrier family 22 member 1 SLC22A1 0.1004
766 Beta-2 adrenergic receptor ADRB2 0.0965
193 Beta-1 adrenergic receptor ADRB1 0.0961
4757 Cytochrome P450 2C9 CYP2C9 0.0959
341 5-hydroxytryptamine 3 receptor HTR3A 0.0947
6107 Cytochrome P450 3A7 CYP3A7 0.0921
6013 Cytochrome P450 2E1 CYP2E1 0.0776
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0726
713 Sodium-dependent dopamine transporter SLC6A3 0.0643
6144 Solute carrier family 22 member 2 SLC22A2 0.0615
6859 Protein S100-A4 S100A4 0.0581
465 Calmodulin CALM1 0.0566
587 Serum albumin ALB 0.0565
131 Synaptic vesicular amine transporter SLC18A2 0.0539
94 5-hydroxytryptamine 4 receptor HTR4 0.0515
1517 Beta-3 adrenergic receptor ADRB3 0.0501
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0496
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0473
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0463
4924 Cytochrome P450 2C8 CYP2C8 0.0442
6147 Solute carrier family 22 member 3 SLC22A3 0.0435
174 Sigma 1-type opioid receptor SIGMAR1 0.0402
6070 Nischarin NISCH 0.0397
3923 Cholinesterase BCHE 0.0385
124 Histamine H2 receptor HRH2 0.0356
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0353
6024 Cytochrome P450 1A1 CYP1A1 0.034
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.034
6030 Cytochrome P450 2B6 CYP2B6 0.0324
3939 Amine oxidase [flavin-containing] B MAOB 0.0318
5718 Cytochrome P450 2A6 CYP2A6 0.0318
118 Organic cation/carnitine transporter 2 SLC22A5 0.0294
164 Histamine H4 receptor HRH4 0.0274
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0274
3947 Xanthine dehydrogenase/oxidase XDH 0.0264
6020 Aldehyde oxidase AOX1 0.0258
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0244
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0236
6151 Monocarboxylate transporter 10 SLC16A10 0.0223
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0221
828 Phenylalanine-4-hydroxylase PAH 0.0211
3109 Phenylalanine-4-hydroxylase phhA 0.0211
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.021
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0195
3810 Catechol O-methyltransferase COMT 0.0195
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0183
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0175
474 Acetylcholinesterase ACHE 0.0172
1898 Cytochrome P450 1B1 CYP1B1 0.0154
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0152
923 Glutamate receptor 3 GRIA3 0.0149
3426 Glutamine synthetase glnA 0.0146
3987 Glutamine synthetase GLUL 0.0146
153 Dopamine beta-hydroxylase DBH 0.014
6432 Transporter snf 0.0135
20 Prostaglandin G/H synthase 1 PTGS1 0.0127
696 Kappa-type opioid receptor OPRK1 0.0112
6106 Cytochrome P450 2C18 CYP2C18 0.011
1636 Trace amine-associated receptor 1 TAAR1 0.011
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0109
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0106
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0104
362 Melatonin receptor type 1B MTNR1B 0.0103
571 Melatonin receptor type 1A MTNR1A 0.0103
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0098
1656 CYP2B protein CYP2B 0.0095
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0095
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0094
921 Glutamate receptor 2 GRIA2 0.0092
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0089
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0088
904 Glutathione S-transferase P GSTP1 0.0085
833 Organic cation/carnitine transporter 1 SLC22A4 0.0083
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0078
847 Mu-type opioid receptor OPRM1 0.0077
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0075
233 Potassium channel subfamily K member 2 KCNK2 0.0072
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0067
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0062
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0062
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0061
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0061
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0061
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0061
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0059
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0056
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0054
776 Bile salt export pump ABCB11 0.0054
3811 Cytochrome P450 19A1 CYP19A1 0.0052
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0051
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0048
467 Delta-type opioid receptor OPRD1 0.0047
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0042
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0042
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0042
694 Matrix protein 2 M 0.0039
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0038
4120 NADPH--cytochrome P450 reductase POR 0.0037
380 Cytochrome P450 17A1 CYP17A1 0.0035
427 Substance-P receptor TACR1 0.0034
1618 High affinity nerve growth factor receptor NTRK1 0.0033
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0032
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0025
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0018
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0017
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0016
1360 Sphingomyelin phosphodiesterase SMPD1 0.0014
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