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Identification
Name Apomorphine
Accession Number DB00714 (APRD00531)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Apomorfin
Apomorphine Hydrochloride
Apomorphine Hydrochloride Hemihydrate
Apomorphinium Chloride Hemihydrate
Apormorphine
L-Apomorphine
VR-040
VR-400
VR004
Salts Not Available
Brand names
Name Company
Apokyn Mylan
Ixense Takeda (discontinued)
Uprima Abbott (discontinued)
Brand mixtures
Brand Name Ingredients
Homeopathic Remedy Thc No. 48 Dps Antimony Trisulfide + Apomorphine + Ipecac + Phosphorus + Pulsatilla
Categories
  • Antiparkinson Agents
  • Antidyskinetics
  • Dopamine Agonists
CAS number 41372-20-7
Weight Average: 267.3224
Monoisotopic: 267.125928793
Chemical Formula C17H17NO2
InChI Key InChIKey=VMWNQDUVQKEIOC-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
Plain Text
IUPAC Name
(9R)-10-methyl-10-azatetracyclo[7.7.1.0^{2,7}.0^{13,17}]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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzylisoquinolines
  • Alkaloids and Alkaloid Derivatives
Substructures
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Naphthalenes
  • Phenylpropenes
  • Benzylisoquinolines
  • Benzene and Derivatives
  • Biphenyl and Derivatives
  • Alkaloids and Alkaloid Derivatives
  • Aliphatic and Aryl Amines
  • Phenanthrenes
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
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.
Pharmacodynamics Apomorphine 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 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
Volume of distribution
  • 123 to 404 L
Protein binding ~50%-albumin
Metabolism Hepatic
Route of elimination Not Available
Half life 40 minutes (range 30 - 60 minutes)
Clearance
  • 223 L/hr
Toxicity LD50=0.6 mmoles/kg (mice, intraperitoneal)
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ipsen biopharm ltd
Packagers
Dosage forms
Form Route Strength
Solution Subcutaneous
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
water solubility 1.66E+004 mg/L Not Available
logP 3.1 Not Available
pKa 8.92 Not Available
Predicted Properties
Property Value Source
water solubility 5.10e-01 g/l ALOGPS
logP 2.51 ALOGPS
logP 2.87 ChemAxon
logS -2.7 ALOGPS
pKa (strongest acidic) 6.58 ChemAxon
pKa (strongest basic) 13.25 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 43.7 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 79.99 ChemAxon
polarizability 29.7 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D07460 Link_out
PubChem Compound 6005 Link_out
PubChem Substance 46508653 Link_out
ChemSpider 5783 Link_out
ChEBI 48538 Link_out
ChEMBL 48538 Link_out
Therapeutic Targets Database DAP000281 Link_out
PharmGKB PA164781163 Link_out
IUPHAR 33 Link_out
Guide to Pharmacology 33 Link_out
RxList http://www.rxlist.com/cgi/generic3/apokyn.htm Link_out
Drugs.com http://www.drugs.com/cdi/apomorphine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Apomorphine Link_out
ATC Codes
  • G04BE07
  • N04BC07
AHFS Codes
  • 28:36.20.08
PDB Entries Not Available
FDA label show (513 KB)
MSDS show (25.8 KB)
Interactions
Drug Interactions
Drug 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

1. D(3) dopamine receptor

Pharmacological action: yes
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P35462 Link_out
Gene: DRD3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P21917 Link_out
Gene: DRD4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Organism class: human
UniProt ID: P18825 Link_out
Gene: ADRA2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out
Gene: ADRA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2C receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21918 Link_out
Gene: DRD5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 1A receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2A receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 2B receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P41595 Link_out
Gene: HTR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out
Gene: ADRA2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out
Gene: DRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 1D receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28221 Link_out
Gene: HTR1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 1B receptor

Pharmacological action: unknown
Actions: agonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28222 Link_out
Gene: HTR1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. D1 dopamine receptor-interacting protein calcyon

Pharmacological action: unknown
Actions: agonist

May have a role in potentiating calcium ion-dependent signaling

Organism class: human
UniProt ID: Q9NYX4 Link_out
Gene: DRD1IP Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19