Identification

Name
Acetophenazine
Accession Number
DB01063  (APRD00462)
Type
Small Molecule
Groups
Approved
Description

Acetophenazine is an antipsychotic drug of moderate-potency. It is used in the treatment of disorganized and psychotic thinking. It is also used to help treat false perceptions (e.g. hallucinations or delusions). It primarily targets the dopamine D2 receptor.

Structure
Thumb
Synonyms
  • Acetophenazine
Product Ingredients
IngredientUNIICASInChI Key
Acetophenazine maleate3P5HNU5JTC5714-00-1NUKVZKPNSKJGBK-SPIKMXEPSA-N
International/Other Brands
Tindal (Schering)
Categories
UNII
8620H6K4QH
CAS number
2751-68-0
Weight
Average: 411.56
Monoisotopic: 411.198047877
Chemical Formula
C23H29N3O2S
InChI Key
WNTYBHLDCKXEOT-UHFFFAOYSA-N
InChI
InChI=1S/C23H29N3O2S/c1-18(28)19-7-8-23-21(17-19)26(20-5-2-3-6-22(20)29-23)10-4-9-24-11-13-25(14-12-24)15-16-27/h2-3,5-8,17,27H,4,9-16H2,1H3
IUPAC Name
1-(10-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl}-10H-phenothiazin-2-yl)ethan-1-one
SMILES
CC(=O)C1=CC=C2SC3=C(C=CC=C3)N(CCCN3CCN(CCO)CC3)C2=C1

Pharmacology

Indication

For the treatment of disorganized and psychotic thinking. Also used to help treat false perceptions (e.g. hallucinations or delusions.)

Pharmacodynamics

Acetophenzine is a phenothiazine antipsychotic intended for the management of schizophrenia and other psychotic disorders.

Mechanism of action

Acetophenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AD(1A) dopamine receptor
antagonist
Human
UAndrogen receptorNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineAcetophenazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineAcetophenazine may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Acetophenazine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Acetophenazine.
AcepromazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Acepromazine.
Food Interactions
Not Available

References

Synthesis Reference
US2985654
General References
  1. Jones GL, Woodbury DM: Spin-label study of phenothiazine interactions with erythrocyte ghost membranes: a possible membrane-mediated antisickling action. J Pharmacol Exp Ther. 1978 Oct;207(1):203-11. [PubMed:702341]
  2. Tam SW, Cook L: Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5618-21. [PubMed:6147851]
External Links
Human Metabolome Database
HMDB0015196
KEGG Compound
C06807
PubChem Compound
17676
PubChem Substance
46507036
ChemSpider
16708
BindingDB
82475
ChEBI
2401
ChEMBL
CHEMBL1085
Therapeutic Targets Database
DAP000844
PharmGKB
PA164781360
Wikipedia
Acetophenazine
ATC Codes
N05AB07 — Acetophenazine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)167-168.5Sherlock, M.H. and Sperber, N.;U .S. Patent 2,985,654; May 23,1961; assigned to Schering Corporation
logP2.62SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0601 mg/mLALOGPS
logP3.48ALOGPS
logP2.65ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)15.46ChemAxon
pKa (Strongest Basic)8.07ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area47.02 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity121.7 m3·mol-1ChemAxon
Polarizability46.68 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9893
Blood Brain Barrier+0.9469
Caco-2 permeable-0.5303
P-glycoprotein substrateSubstrate0.846
P-glycoprotein inhibitor IInhibitor0.8809
P-glycoprotein inhibitor IIInhibitor0.6834
Renal organic cation transporterInhibitor0.5248
CYP450 2C9 substrateNon-substrate0.6788
CYP450 2D6 substrateSubstrate0.7697
CYP450 3A4 substrateNon-substrate0.644
CYP450 1A2 substrateInhibitor0.8354
CYP450 2C9 inhibitorNon-inhibitor0.9186
CYP450 2D6 inhibitorInhibitor0.8979
CYP450 2C19 inhibitorNon-inhibitor0.8746
CYP450 3A4 inhibitorNon-inhibitor0.7426
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.817
CarcinogenicityNon-carcinogens0.891
BiodegradationNot ready biodegradable0.9893
Rat acute toxicity2.7720 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8509
hERG inhibition (predictor II)Inhibitor0.7117
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0h2f-7962200000-29f2e9055979e0add70b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / Acetophenones / Aryl alkyl ketones / N-alkylpiperazines / 1,4-thiazines / Trialkylamines / 1,2-aminoalcohols / Azacyclic compounds / Primary alcohols
show 3 more
Substituents
Phenothiazine / Alkyldiarylamine / Diarylthioether / Acetophenone / Aryl thioether / Tertiary aliphatic/aromatic amine / Aryl ketone / Aryl alkyl ketone / N-alkylpiperazine / Para-thiazine
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, N-(2-hydroxyethyl)piperazine, N-alkylpiperazine (CHEBI:2401)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
  4. Tam SW, Cook L: Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5618-21. [PubMed:6147851]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Bisson WH, Cheltsov AV, Bruey-Sedano N, Lin B, Chen J, Goldberger N, May LT, Christopoulos A, Dalton JT, Sexton PM, Zhang XK, Abagyan R: Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11927-32. Epub 2007 Jul 2. [PubMed:17606915]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:51