Acepromazine is one of the phenothiazine derivative psychotropic drugs, used little in humans, however frequently in animals as a sedative and antiemetic.

Structure

Similar Structures

Synonyms

1-[10-(3-dimethylamino-propyl)-10H-phenothiazin-2-yl]-ethanone
10-(3-dimethylaminopropyl)phenothiazin-3-yl methyl ketone
10-(3-dimethylaminopropyl)phenothiazine-3-ethylone
Acepromazina
Acepromazine
Acepromazinum
Acetazine
Acetopromazine
Acetylpromazine

External IDs

1522 CB / AY-57,062 / SV-1522 / WY-1172

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Acepromazine maleate	37862HP2OM	3598-37-6	FQRHOOHLUYHMGG-BTJKTKAUSA-N

International/Other Brands

Concentrat vo34

Categories

UNII

54EJ303F0R

CAS number

61-00-7

Weight

Average: 326.456
Monoisotopic: 326.145284026

Chemical Formula

C₁₉H₂₂N₂OS

InChI Key

NOSIYYJFMPDDSA-UHFFFAOYSA-N

InChI

InChI=1S/C19H22N2OS/c1-14(22)15-9-10-19-17(13-15)21(12-6-11-20(2)3)16-7-4-5-8-18(16)23-19/h4-5,7-10,13H,6,11-12H2,1-3H3

IUPAC Name

1-{10-[3-(dimethylamino)propyl]-10H-phenothiazin-2-yl}ethan-1-one

SMILES

CN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(C=C2)C(C)=O

Pharmacology

Indication

Acepromazine was first used in humans in the 1950s as an antipsychotic agent. It is now rarely used in humans. Acepromazine is frequently used in animals as a sedative and antiemetic. Its principal value is in quietening and calming anxious animals.

Pharmacodynamics

Acepromazine is one of the phenothiazine derivative psychotropic drugs. Acepromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Acepromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.

Mechanism of action

Acepromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).

Target	Actions	Organism
AD(2) dopamine receptor	antagonist	Humans
AD(1A) dopamine receptor	antagonist	Humans
A5-hydroxytryptamine receptor 2A	antagonist	Humans
A5-hydroxytryptamine receptor 1A	antagonist	Humans
UAlpha-1A adrenergic receptor	antagonist	Humans
UAlpha-1B adrenergic receptor	antagonist	Humans

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

3 hours in horses.

Clearance

Not Available

Toxicity

Agitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, restlessness

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	The risk or severity of adverse effects can be increased when Acepromazine is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of adverse effects can be increased when Acepromazine is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid	The risk or severity of hypertension can be increased when Acepromazine is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazole	The risk or severity of hypertension can be increased when Acepromazine is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamine	The therapeutic efficacy of Acepromazine can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	The therapeutic efficacy of Acepromazine can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The therapeutic efficacy of Acepromazine can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin	The risk or severity of adverse effects can be increased when Acepromazine is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine	The risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Acepromazine.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of adverse effects can be increased when Acepromazine is combined with 5-methoxy-N,N-dimethyltryptamine.

Food Interactions

Avoid alcohol
Take with food to reduce irritation

References

General References

Not Available

External Links

Human Metabolome Database: HMDB0015552
KEGG Drug: D07065
PubChem Compound: 6077
PubChem Substance: 46508205
ChemSpider: 5852
BindingDB: 50131719
ChEBI: 44932
ChEMBL: CHEMBL39560
PharmGKB: PA164783999
HET: PMZ
Wikipedia: Acepromazine

ATC Codes

N05AA04 — Acepromazine

PDB Entries

1lvj

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

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	< 25 °C	PhysProp
boiling point (°C)	230 °C at 5.00E-01 mm Hg	PhysProp

Predicted Properties

Property	Value	Source
Water Solubility	0.0098 mg/mL	ALOGPS
logP	4.32	ALOGPS
logP	3.49	ChemAxon
logS	-4.5	ALOGPS
pKa (Strongest Acidic)	16.06	ChemAxon
pKa (Strongest Basic)	8.5	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	23.55 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	99.35 m³·mol^-1	ChemAxon
Polarizability	37.17 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9852
Blood Brain Barrier	+	0.9844
Caco-2 permeable	+	0.8203
P-glycoprotein substrate	Substrate	0.8092
P-glycoprotein inhibitor I	Inhibitor	0.8563
P-glycoprotein inhibitor II	Inhibitor	0.857
Renal organic cation transporter	Inhibitor	0.7087
CYP450 2C9 substrate	Non-substrate	0.7438
CYP450 2D6 substrate	Substrate	0.8618
CYP450 3A4 substrate	Substrate	0.6468
CYP450 1A2 substrate	Inhibitor	0.9106
CYP450 2C9 inhibitor	Non-inhibitor	0.9319
CYP450 2D6 inhibitor	Inhibitor	0.9115
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.9105
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.7333
Ames test	Non AMES toxic	0.849
Carcinogenicity	Non-carcinogens	0.9292
Biodegradation	Not ready biodegradable	0.9829
Rat acute toxicity	2.7963 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9537
hERG inhibition (predictor II)	Inhibitor	0.7813

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (7.84 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
GC-MS Spectrum - EI-B	GC-MS	splash10-0a4i-9110000000-bd29071c9502d119fa54
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-004i-0009000000-ba8f0be449800ec10cf1
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-002r-9025000000-028fcf239ba77c5d26d0
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-000i-9060000000-33b3210f75c9aa6899f3
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0abi-9180000000-9b10f7d22435e199c283
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0a4i-9670000000-0c65cbf1672ae4899236

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 / 1,4-thiazines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents: Phenothiazine / Alkyldiarylamine / Diarylthioether / Acetophenone / Aryl thioether / Tertiary aliphatic/aromatic amine / Aryl alkyl ketone / Aryl ketone / Para-thiazine / Benzenoid
Molecular Framework: Aromatic heteropolycyclic compounds
External Descriptors: phenothiazines, tertiary amino compound, methyl ketone, aromatic ketone (CHEBI:44932)

Targets

Details1. D(2) dopamine receptor

Kind: Protein
Organism: Humans
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

Oades RD, Rao ML, Bender S, Sartory G, Muller BW: Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. Behav Pharmacol. 2000 Jun;11(3-4):317-30. [PubMed:11103886]
Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, He L: Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. Epub 2004 Dec 2. [PubMed:15694263]
Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L: Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006 Aug;27(8):966-70. [PubMed:16867246]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. doi: 10.3371/CSRP.4.1.5. [PubMed:20643630]

Details2. D(1A) dopamine receptor

Kind: Protein
Organism: Humans
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

Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E: Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994 Jul;19(4):265-9. [PubMed:7918347]

Details3. 5-hydroxytryptamine receptor 2A

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

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-iodop...
Gene Name: HTR2A
Uniprot ID: P28223
Uniprot Name: 5-hydroxytryptamine receptor 2A
Molecular Weight: 52602.58 Da

References

Kusumi I, Takahashi Y, Suzuki K, Kameda K, Koyama T: Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain. J Neural Transm (Vienna). 2000;107(3):295-302. [PubMed:10821438]
Yamada J, Sugimoto Y, Horisaka K: Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice. Biol Pharm Bull. 1995 Nov;18(11):1580-3. [PubMed:8593484]

Details4. 5-hydroxytryptamine receptor 1A

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

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. Ligand binding causes a conformation change that triggers...
Gene Name: HTR1A
Uniprot ID: P08908
Uniprot Name: 5-hydroxytryptamine receptor 1A
Molecular Weight: 46106.335 Da

References

Cosi C, Koek W: Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells. Eur J Pharmacol. 2001 Dec 14;433(1):55-62. [PubMed:11755134]
Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verriele L, Audinot V, Millan MJ: Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol. 1998 Aug 21;355(2-3):245-56. [PubMed:9760039]

Details5. Alpha-1A adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Protein heterodimerization activity
Specific Function: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name: ADRA1A
Uniprot ID: P35348
Uniprot Name: Alpha-1A adrenergic receptor
Molecular Weight: 51486.005 Da

References

Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [PubMed:15695070]

Details6. Alpha-1B adrenergic receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Protein heterodimerization activity
Specific Function: This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name: ADRA1B
Uniprot ID: P35368
Uniprot Name: Alpha-1B adrenergic receptor
Molecular Weight: 56835.375 Da

References

Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [PubMed:15695070]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

References

Kitamura K, Omran AA, Nagata C, Kamijima Y, Tanaka R, Takegami S, Kitade T: Effects of inorganic ions on the binding of triflupromazine and chlorpromazine to bovine serum albumin studied by spectrometric methods. Chem Pharm Bull (Tokyo). 2006 Jul;54(7):972-6. [PubMed:16819214]
Rukhadze MD, Bezarashvili GS, Sidamonidze NS, Tsagareli SK: Investigation of binding process of chlorpromazine to bovine serum albumin by means of passive and active experiments. Biomed Chromatogr. 2001 Oct;15(6):365-73. [PubMed:11559920]
Silva D, Cortez CM, Louro SR: Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin. Braz J Med Biol Res. 2004 Jul;37(7):963-8. Epub 2004 Jun 22. [PubMed:15264002]

Drug created on August 29, 2007 14:12 / Updated on April 09, 2019 10:11

Acepromazine

Identification

Structure for Acepromazine (DB01614)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

References

References

References

Carriers

References