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Record Information
Creation Date2014-08-29 04:49:13 UTC
Update Date2014-12-24 20:26:35 UTC
Accession NumberT3D4015
Common NameProtopine
ClassSmall Molecule
DescriptionProtopine is a benzylisoquinoline alkaloid occurring in opium poppies and other plants of the family papaveraceae. It has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an opioid analgesic.
Compound Type
  • Amine
  • Ester
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Chemical FormulaC20H19NO5
Average Molecular Mass353.369 g/mol
Monoisotopic Mass353.126 g/mol
CAS Registry Number130-86-9
IUPAC Name15-methyl-7,9,19,21-tetraoxa-15-azapentacyclo[⁴,¹².0⁶,¹⁰.0¹⁸,²²]tetracosa-1(17),4(12),5,10,18(22),23-hexaen-3-one
Traditional Nameprotopine
InChI IdentifierInChI=1S/C20H19NO5/c1-21-5-4-13-7-18-19(25-10-24-18)8-14(13)16(22)6-12-2-3-17-20(15(12)9-21)26-11-23-17/h2-3,7-8H,4-6,9-11H2,1H3
Chemical Taxonomy
Description belongs to the class of organic compounds known as protopine alkaloids. These are alkaloids with a structure based on a tricyclic protopine formed by oxidative ring fission of protoberberine N-metho salts.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassProtopine alkaloids
Sub ClassNot Available
Direct ParentProtopine alkaloids
Alternative Parents
  • Protopine skeleton
  • Benzodioxole
  • Aryl ketone
  • Aryl alkyl ketone
  • Aralkylamine
  • Benzenoid
  • Ketone
  • Tertiary amine
  • Tertiary aliphatic amine
  • Acetal
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Amine
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
AppearanceWhite powder.
Experimental Properties
Melting Point208°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
Water Solubility0.2 g/LALOGPS
pKa (Strongest Acidic)15.82ChemAxon
pKa (Strongest Basic)4.95ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area57.23 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity94.57 m³·mol⁻¹ChemAxon
Polarizability36.68 ųChemAxon
Number of Rings5ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-004r-2931000000-d14db9f8fbba357a7cea2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-004r-2931000000-d14db9f8fbba357a7cea2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00ri-2049000000-c70fb92c70c89eb315592017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0f79-0936000000-da2afff6dba215da666a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-0931000000-3ae8ba25a400b3cfc3362017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-0009000000-d474e4da85bfe6b8622e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-0009000000-c77daec49f175e0080d32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udi-0629000000-f410a01812829c61b1b52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-0921000000-cb2a7100722bf81f462f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-0930000000-e740d177ef096526ca532017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-000j-0932000000-899dc6a90055430abee22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0009000000-1833ae0a6ab82f156d512017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udr-0938000000-8a5ae3db2af3946a0e752017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0920000000-925c965ff2b76b30d02f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0f79-0944000000-e1624142a49564f32b992017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-000i-0910000000-79485782e2b17a1fccef2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-000i-0931000000-a9d401bee935049397de2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-000i-0920000000-092e042fc79ca310c1932021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 6V, Positivesplash10-000i-0941000000-1fdf197d94d08c882c082021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0009000000-aab71a61504570b7beeb2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0udr-0928000000-60509c382ac86776f91c2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-000i-0920000000-925c965ff2b76b30d02f2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0009000000-0089e0012db766e235292016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udj-0509000000-ed54f57036aee6ac913c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004j-1900000000-e130dfa9e240571ed4e02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-400e98b52794a7bf4fbd2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0009000000-71833c50697c0a4e532c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-9658000000-c8824149cc8b247dcb6f2016-08-03View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0002-2910000000-c237219498d206631a062014-09-20View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityProtopine has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an analgesic. It is one of the compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Protopine can selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Classical antihistaminics antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. Protopine can also function as platelet aggregation inhibitors which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Protopine inhibits the contractility of isolated cardiac papillary muscles and the proliferation of vascular smooth muscle cells induced by endothelin. It also shortens action potential duration and prolongs the effective refractory period in guinea pig cardiac papillary muscles. The protective effect on rat heart from ischemia_reperfusion damage and the relaxation of rat thoracic aorta induced by protopine have been related to the inhibition of Ca2+ influx through both voltage- and receptor-operated Ca2+ channels. Protopine has been the focus of a large number of biological studies in which they both exhibited, for instance, anti-parasitic activity and only weak cytotoxicity in comparison with other types of isoquinoline alkaloids. Protopine was found to be cytoprotective against oxidative stress induced cell death in vitro. The alkaloid was shown to have anti-arrhythmic, anti-thrombotic, anti-inflammatory, and hepatoprotective effects in animal models. The biological activity of protopine may be associated with its ability to inhibit calcium, sodium, and potassium channels. (PMID:15588728; PMID:21419197; L2104)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIt has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an opioid analgesic.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
PubChem Compound ID4970
ChemSpider ID4799
UniProt IDNot Available
ChEBI ID16415
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
Synthesis ReferenceRueffer, M.; Zenk, M. H. Enzymatic formation of protopines by a microsomal cytochrome P-450 system of Corydalis vaginans. Tetrahedron Letters (1987), 28(44), 5307-10.
General References
  1. Paul LD, Maurer HH: Studies on the metabolism and toxicological detection of the Eschscholtzia californica alkaloids californine and protopine in urine using gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jun 5;789(1):43-57. [12726842 ]
  2. Wynne PM, Vine JH, Amiet RG: Protopine alkaloids in horse urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Nov 5;811(1):85-91. [15458726 ]
  3. Jiang B, Cao K, Wang R: Inhibitory effect of protopine on K(ATP) channel subunits expressed in HEK-293 cells. Eur J Pharmacol. 2004 Dec 15;506(2):93-100. [15588728 ]
  4. pubchem [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available