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Identification
NameAcetophenazine
Accession NumberDB01063  (APRD00462)
TypeSmall Molecule
GroupsApproved
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
SynonymLanguageCode
AcetophenazineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
TindalSchering
Brand mixturesNot Available
Categories
CAS number2751-68-0
WeightAverage: 411.56
Monoisotopic: 411.198047877
Chemical FormulaC23H29N3O2S
InChI KeyWNTYBHLDCKXEOT-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiazines
SubclassPhenothiazines
Direct parentPhenothiazines
Alternative parentsAcetophenones; Benzoyl Derivatives; Piperazines; Diazinanes; Tertiary Amines; Ketones; Enolates; Primary Alcohols; Polyamines; Thioethers
Substituentsacetophenone; benzoyl; 1,4-diazinane; benzene; piperazine; tertiary amine; ketone; enolate; thioether; polyamine; primary alcohol; alcohol; carbonyl group; amine; organonitrogen compound
Classification descriptionThis compound belongs to the 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.
Pharmacology
IndicationFor the treatment of disorganized and psychotic thinking. Also used to help treat false perceptions (e.g. hallucinations or delusions.)
PharmacodynamicsAcetophenzine is a phenothiazine antipsychotic intended for the management of schizophrenia and other psychotic disorders.
Mechanism of actionAcetophenazine 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9893
Blood Brain Barrier + 0.9469
Caco-2 permeable - 0.5303
P-glycoprotein substrate Substrate 0.846
P-glycoprotein inhibitor I Inhibitor 0.8809
P-glycoprotein inhibitor II Inhibitor 0.6834
Renal organic cation transporter Inhibitor 0.5248
CYP450 2C9 substrate Non-substrate 0.6788
CYP450 2D6 substrate Substrate 0.7697
CYP450 3A4 substrate Non-substrate 0.644
CYP450 1A2 substrate Inhibitor 0.8354
CYP450 2C9 substrate Non-inhibitor 0.9186
CYP450 2D6 substrate Inhibitor 0.8979
CYP450 2C19 substrate Non-inhibitor 0.8746
CYP450 3A4 substrate Non-inhibitor 0.7426
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5
Ames test Non AMES toxic 0.817
Carcinogenicity Non-carcinogens 0.891
Biodegradation Not ready biodegradable 0.9893
Rat acute toxicity 2.7720 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8509
hERG inhibition (predictor II) Inhibitor 0.7117
Pharmacoeconomics
Manufacturers
  • Schering corp sub schering plough corp
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point167-168.5Sherlock, 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 Solubility0.0601ALOGPS
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
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US2985654
General Reference
  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
  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
External Links
ResourceLink
KEGG CompoundC06807
ChEBI2401
ChEMBLCHEMBL1085
Therapeutic Targets DatabaseDAP000844
PharmGKBPA164781360
WikipediaAcetophenazine
ATC CodesN05AB07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
BromocriptineThe phenothiazine decreases the effect of bromocriptine
CisaprideIncreased risk of cardiotoxicity and arrhythmias
DexfenfluramineDecreased anorexic effect, may increase psychotic symptoms
DiethylpropionDecreased anorexic effect, may increase psychotic symptoms
FenfluramineDecreased anorexic effect, may increase psychotic symptoms
GuanethidineAcetophenazine may decrease the effect of guanethidine.
MazindolDecreased anorexic effect, may increase psychotic symptoms
PhentermineDecreased anorexic effect, may increase psychotic symptoms
PhenylpropanolamineDecreased anorexic effect, may increase psychotic symptoms
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Acetophenazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
TerfenadineIncreased risk of cardiotoxicity and arrhythmias
TetrabenazineMay cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
TrimethobenzamideTrimethobenzamide and Acetophenazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineThe antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Acetophenazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Acetophenazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food InteractionsNot Available

Targets

1. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

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

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
  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
  3. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed
  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
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

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

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
  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

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Drug created on June 13, 2005 07:24 / Updated on March 27, 2014 10:27