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Identification
NameApomorphine
Accession NumberDB00714  (APRD00531)
TypeSmall Molecule
GroupsApproved, Investigational
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
Thumb
Synonyms
SynonymLanguageCode
(-)-10,11-DihydroxyaporphineNot AvailableNot Available
(−)-10,11-dihydroxyaporphineNot AvailableNot Available
(6AR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diolNot AvailableNot Available
(R)-5,6,6a,7-Tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,11-diolNot AvailableNot Available
ApomorphinGermanNot Available
R-(-)-ApomorphineNot AvailableNot Available
R-(−)-apomorphineNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apokyninjection30 mg/3mLsubcutaneousTercica, Inc.2004-07-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Apokyninjection30 mg/3mLsubcutaneousUs World Meds, Llc2004-07-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
IxenseTakeda (discontinued)
SpontaneNot Available
UprimaAbbott (discontinued)
Brand mixtures
Brand NameIngredients
Homeopathic Remedy Thc No. 48 DpsAntimony Trisulfide + Apomorphine + Ipecac + Phosphorus + Pulsatilla
Salts
Name/CASStructureProperties
Apomorphine Hydrochloride
Thumb
  • InChI Key: SKYZYDSNJIOXRL-BTQNPOSSSA-N
  • Monoisotopic Mass: 303.102606532
  • Average Mass: 303.783
DBSALT000818
Categories
CAS number41372-20-7
WeightAverage: 267.3224
Monoisotopic: 267.125928793
Chemical FormulaC17H17NO2
InChI KeyVMWNQDUVQKEIOC-CYBMUJFWSA-N
InChI
InChI=1S/C17H17NO2/c1-18-8-7-10-3-2-4-12-15(10)13(18)9-11-5-6-14(19)17(20)16(11)12/h2-6,13,19-20H,7-9H2,1H3/t13-/m1/s1
IUPAC Name
(9R)-10-methyl-10-azatetracyclo[7.7.1.0²,⁷.0¹³,¹⁷]heptadeca-1(16),2(7),3,5,13(17),14-hexaene-3,4-diol
SMILES
[H][C@]12CC3=C(C(O)=C(O)C=C3)C3=CC=CC(CCN1C)=C23
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aporphines. These are quinoline alkaloids containing the dibenzo[de,g]quinoline ring system or a dehydrogenated derivative thereof.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassAporphines
Sub ClassNot Available
Direct ParentAporphines
Alternative Parents
Substituents
  • Aporphine
  • Benzylisoquinoline
  • Phenanthrene
  • Benzoquinoline
  • 1-naphthol
  • 2-naphthol
  • Tetrahydroisoquinoline
  • Quinoline
  • Naphthalene
  • 1,2-diphenol
  • Aralkylamine
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the acute, intermittent treatment of hypomobility, off episodes (end-of-dose wearing off and unpredictable on/off episodes) associated with advanced Parkinson's disease.
PharmacodynamicsApomorphine is a type of dopaminergic agonist, a morphine derivative which primarily affects the hypothalamic region of the brain. Drugs containing this substance are sometimes used in the treatment of Parkinson's disease or erectile dysfunction. In higher doses it is a highly effective emetic.
Mechanism of actionThe 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.
Absorption100% following subcutaneous administration
Volume of distribution
  • 123 to 404 L
Protein binding~50%-albumin
Metabolism

Hepatic

Route of eliminationNot Available
Half life40 minutes (range 30 - 60 minutes)
Clearance
  • 223 L/hr
ToxicityLD50=0.6 mmoles/kg (mice, intraperitoneal)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9816
Blood Brain Barrier+0.9401
Caco-2 permeable+0.777
P-glycoprotein substrateSubstrate0.8501
P-glycoprotein inhibitor INon-inhibitor0.8781
P-glycoprotein inhibitor IINon-inhibitor0.964
Renal organic cation transporterInhibitor0.6477
CYP450 2C9 substrateNon-substrate0.7577
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7039
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 substrateNon-inhibitor0.9146
CYP450 2D6 substrateNon-inhibitor0.9084
CYP450 2C19 substrateNon-inhibitor0.8718
CYP450 3A4 substrateNon-inhibitor0.9156
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9262
Ames testAMES toxic0.6775
CarcinogenicityNon-carcinogens0.9736
BiodegradationNot ready biodegradable0.8928
Rat acute toxicity2.6446 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6544
hERG inhibition (predictor II)Inhibitor0.7734
Pharmacoeconomics
Manufacturers
  • Ipsen biopharm ltd
Packagers
Dosage forms
FormRouteStrength
Injectionsubcutaneous30 mg/3mL
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility1.66E+004 mg/LNot Available
logP3.1Not Available
pKa8.92Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.51 mg/mLALOGPS
logP2.51ALOGPS
logP2.87ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)6.58ChemAxon
pKa (Strongest Basic)13.25ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area43.7 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.99 m3·mol-1ChemAxon
Polarizability29.7 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Narayanasamy Gurusamy, “Process for Making Apomorphine and Apocodeine.” U.S. Patent US20100228032, issued September 09, 2010.

US20100228032
General Reference
  1. Matsumoto K, Yoshida M, Andersson KE, Hedlund P: Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum. Br J Pharmacol. 2005 Sep;146(2):259-67. Pubmed
  2. SCHWAB RS, AMADOR LV, LETTVIN JY: Apomorphine in Parkinson’s disease. Trans Am Neurol Assoc. 1951;56:251-3. Pubmed
  3. Cotzias GC, Papavasiliou PS, Fehling C, Kaufman B, Mena I: Similarities between neurologic effects of L-dipa and of apomorphine. N Engl J Med. 1970 Jan 1;282(1):31-3. Pubmed
  4. Corsini GU, Del Zompo M, Gessa GL, Mangoni A: Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson’s disease. Lancet. 1979 May 5;1(8123):954-6. Pubmed
  5. Chaudhuri KR, Clough C: Subcutaneous apomorphine in Parkinson’s disease. BMJ. 1998 Feb 28;316(7132):641. Pubmed
External Links
ATC CodesG04BE07N04BC07
AHFS Codes
  • 28:36.20.08
PDB EntriesNot Available
FDA labelDownload (513 KB)
MSDSDownload (25.8 KB)
Interactions
Drug Interactions
Drug
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
EntacaponeEntacapone increases the effect and toxicity of the sympathomimetic, apomorphine.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
PaliperidoneThe 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.
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
ThiothixeneMay 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.
ToremifeneAdditive 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.
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
ZuclopenthixolAdditive 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 InteractionsNot Available

Targets

1. D(3) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(3) dopamine receptor P35462 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. D(4) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(4) dopamine receptor P21917 Details

References:

  1. 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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  4. 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
  5. 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
  6. 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

3. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. 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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. 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
  4. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  5. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed
  6. 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
  7. 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
  8. 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

4. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

5. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

6. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

7. D(1B) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
D(1B) dopamine receptor P21918 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

8. 5-hydroxytryptamine receptor 1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

9. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

10. 5-hydroxytryptamine receptor 2B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2B P41595 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

11. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

12. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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
  3. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed
  4. Lam YW: Clinical pharmacology of dopamine agonists. Pharmacotherapy. 2000 Jan;20(1 Pt 2):17S-25S. Pubmed

13. 5-hydroxytryptamine receptor 1D

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1D P28221 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

14. 5-hydroxytryptamine receptor 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1B P28222 Details

References:

  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. Pubmed

15. Neuron-specific vesicular protein calcyon

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Neuron-specific vesicular protein calcyon Q9NYX4 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11