Prochlorperazine (T3D2789)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2009-07-21 20:26:53 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2789
Identification
Common NameProchlorperazine
ClassSmall Molecule
DescriptionProchlorperazine is only found in individuals that have used or taken this drug. It is a phenothiazine antipsychotic used principally in the treatment of nausea; vomiting; and vertigo. It is more likely than chlorpromazine to cause extrapyramidal disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p612) The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its antidopaminergic effects. Prochlorperazine blocks the D2 somatodendritic autoreceptor, resulting in the blockade of postsynaptic dopamine receptors in the mesolimbic system and an increased dopamine turnover. Prochlorperazine also has anti-emetic effects, which can be attributed to dopamine blockade in the chemoreceptor trigger zone. Prochlorperazine also blocks anticholinergic and alpha-adrenergic receptors, the blockade of alpha(1)-adrenergic receptors resulting in sedation, muscle relaxation, and hypotension.
Compound Type
  • Amine
  • Antiemetic
  • Antipsychotic Agent
  • Dopamine Antagonist
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Organochloride
  • Phenothiazine
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2-Chloro-10-(3-(1-methyl-4-piperazinyl)propyl)-phenothiazine
2-Chloro-10-(3-(4-methyl-1-piperazinyl)propyl)phenothiazine
3-Chloro-10-(3-(1-methyl-4-piperazinyl)propyl)phenothiazine
3-Chloro-10-(3-(4-methyl-1-piperazinyl)propyl)phenothiazine
Buccastem
Capazine
Chlormeprazine
Chloro-3 (N-methylpiperazinyl-3 propyl)-10 phenothiazine
Chloropernazine
Chlorperazine
Compazine
Compro
Emetiral
N-(gamma-(4'-Methylpiperazinyl-1')propyl)-3-chlorophenothiazine
Prochloroperazine
Prochlorpemazine
Prochlorperazin
Prochlorpérazine
Prochlorperazine edisylate
Prochlorperazine maleate
Prochlorperazinum
Prochlorpermazine
Prochlorpromazine
Procloperazine
Proclorperazina
Proclorperazine
Stemetil
Stemzine
Volimin
Chemical FormulaC20H24ClN3S
Average Molecular Mass373.943 g/mol
Monoisotopic Mass373.138 g/mol
CAS Registry Number58-38-8
IUPAC Name2-chloro-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine
Traditional Namecompro
SMILESCN1CCN(CCCN2C3=CC=CC=C3SC3=C2C=C(Cl)C=C3)CC1
InChI IdentifierInChI=1S/C20H24ClN3S/c1-22-11-13-23(14-12-22)9-4-10-24-17-5-2-3-6-19(17)25-20-8-7-16(21)15-18(20)24/h2-3,5-8,15H,4,9-14H2,1H3
InChI KeyInChIKey=WIKYUJGCLQQFNW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Aryl thioether
  • Tertiary aliphatic/aromatic amine
  • N-alkylpiperazine
  • N-methylpiperazine
  • Para-thiazine
  • Aryl chloride
  • Aryl halide
  • 1,4-diazinane
  • Benzenoid
  • Piperazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Thioether
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point228°C
Boiling PointNot Available
Solubility15 mg/L (at 24°C)
LogP4.88
Predicted Properties
PropertyValueSource
Water Solubility0.011 g/LALOGPS
logP4.67ALOGPS
logP4.38ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)8.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.72 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity109.81 m³·mol⁻¹ChemAxon
Polarizability41.77 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-01vo-9853000000-ba88fedd94e150c34e1a2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0229-7933000000-4e14a9a9728c361941d32017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-01vo-9853000000-ba88fedd94e150c34e1a2018-05-18View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0229-7933000000-4e14a9a9728c361941d32018-05-18View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-06xt-9553000000-7c5cfdffb1424ab9b4c32017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00fr-0219000000-abf2f9a1f6a1efb497b82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-01vo-1913000000-18dc04b2a841732cef462021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0119000000-c5080d81978309713b432016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dl-3759000000-27beb72c9655a5a102922016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05fr-9641000000-e1d8ff01b979f368bc222016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0009000000-237f2504c3b8b858f4202016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03k9-0093000000-596171d19953284e7c672016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001j-6790000000-18250cf634dd842e2d162016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0009000000-b7096763c7649cee63202021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0019000000-a9bd62cc7ad7a33ce8ea2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-9073000000-a0220d70775ae81553092021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0009000000-2aca52d377070d2c9d912021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dl-0908000000-0cbc070d6e31e1a308b02021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-08n9-9621000000-82835cd472af493a67f32021-09-24View Spectrum
MSMass Spectrum (Electron Ionization)splash10-022c-9752000000-533ac31876b44d82f2aa2014-09-20View Spectrum
Toxicity Profile
Route of ExposureIntravenous, Oral, Rectal. Rapidly absorbed following oral administration.
Mechanism of ToxicityThe mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its antidopaminergic effects. Prochlorperazine blocks the D2 somatodendritic autoreceptor, resulting in the blockade of postsynaptic dopamine receptors in the mesolimbic system and an increased dopamine turnover. Prochlorperazine also has anti-emetic effects, which can be attributed to dopamine blockade in the chemoreceptor trigger zone. Prochlorperazine also blocks anticholinergic and alpha-adrenergic receptors, the blockade of alpha(1)-adrenergic receptors resulting in sedation, muscle relaxation, and hypotension.
MetabolismHepatic. Undergoes metabolism in the gastric mucosa and on first pass through the liver, CYP2D6 and/or CYP3A4. Half Life: 6 to 8 hours
Toxicity ValuesLD50=400mg/kg (orally in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the symptomatic management of psychotic disorders, short term management of nonpsychotic anxiety in patients with generalized anxiety disorder, and for the control of severe nausea and vomiting of various causes.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus; LD50=400mg/kg (orally in mice)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00433
HMDB IDHMDB14577
PubChem Compound ID4917
ChEMBL IDCHEMBL728
ChemSpider ID4748
KEGG IDC07403
UniProt IDNot Available
OMIM ID
ChEBI ID8435
BioCyc IDCPD-10433
CTD IDNot Available
Stitch IDProchlorperazine
PDB IDP77
ACToR IDNot Available
Wikipedia LinkProchlorperazine
References
Synthesis Reference

DrugSyn.org

MSDSLink
General References
  1. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. D(2) dopamine receptor
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Roberge RJ: Antiemetic-related dystonic reaction unmasked by removal of a scopolamine transdermal patch. J Emerg Med. 2006 Apr;30(3):299-302. [16677982 ]
  3. Hamik A, Peroutka SJ: Differential interactions of traditional and novel antiemetics with dopamine D2 and 5-hydroxytryptamine3 receptors. Cancer Chemother Pharmacol. 1989;24(5):307-10. [2527092 ]
  4. Vinson DR: Development of a simplified instrument for the diagnosis and grading of akathisia in a cohort of patients receiving prochlorperazine. J Emerg Med. 2006 Aug;31(2):139-45. [17044574 ]
Target Details
2. 5-hydroxytryptamine receptor 2A
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
References
  1. Tsuchihashi H, Sasaki T, Kojima S, Nagatomo T: Binding of [3H]haloperidol to dopamine D2 receptors in the rat striatum. J Pharm Pharmacol. 1992 Nov;44(11):911-4. [1361536 ]
  2. Herrick-Davis K, Grinde E, Teitler M: Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther. 2000 Oct;295(1):226-32. [10991983 ]
Target Details
3. Histamine H1 receptor
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.019 uMNot AvailableBindingDB 50292708
References
  1. Tsuchihashi H, Sasaki T, Kojima S, Nagatomo T: Binding of [3H]haloperidol to dopamine D2 receptors in the rat striatum. J Pharm Pharmacol. 1992 Nov;44(11):911-4. [1361536 ]
  2. Richelson E, Nelson A: Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204. [6149136 ]
Target Details
4. 5-hydroxytryptamine receptor 2C
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.122 uMNot AvailableBindingDB 50292708
References
  1. Herrick-Davis K, Grinde E, Teitler M: Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther. 2000 Oct;295(1):226-32. [10991983 ]
Target Details
5. Alpha-2A adrenergic receptor
General Function:
Thioesterase binding
Specific Function:
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.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.7 uMNot AvailableBindingDB 50292708
References
  1. Richelson E, Nelson A: Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204. [6149136 ]
Target Details
6. D(1A) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
7. Muscarinic acetylcholine receptor M2
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.54 uMNot AvailableBindingDB 50292708
References
  1. Richelson E, Nelson A: Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204. [6149136 ]
Target Details
8. Cytochrome b-245 heavy chain
General Function:
Voltage-gated ion channel activity
Specific Function:
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.
Gene Name:
CYBB
Uniprot ID:
P04839
Molecular Weight:
65335.415 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5050 uMNot AvailableBindingDB 50292708
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Target Details
9. Solute carrier family 22 member 1
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5049.6 uMNot AvailableBindingDB 50292708
References
  1. Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. doi: 10.1021/jm8003152. Epub 2008 Sep 13. [18788725 ]