General
Preferred name
PROCHLORPERAZINE
Synonyms
PROCHLORPERAZINE EDISYLATE ()
Prochlorperazine dimaleate ()
Buccastem ()
Vertigon ()
Buccastem M ()
Proziere ()
Compazine ()
Prochlorperazine (D8 dimeleate) ()
Prochlorperazine D8 ()
Prochlorperazine dimaleate salt ()
Prochlorperazin ()
Capazine ()
Stemetil ()
PROCHLORPERAZINE MALEATE ()
10H-Phenothiazine, 2-chloro-10-[3-(4-methyl-1-piperazinyl)propyl- ()
Prochlorperazin, Compazine, Capazine, Stemetil ()
Stemetil Eff ()
Compro ()
Prochlorperazine Mesilate ()
Prochlorperazine mesylate ()
Prochlorperazine ()
NSC-757299 ()
Prochlorperazine edisylate salt ()
Prochlorperazine Ethanedisulfonate ()
Prochlorperazine edisilate ()
Procomp ()
Prochlorperazine (maleate) ()
Prochlorperazine-d8 (hydrochloride) ()
P&D ID
PD003507
CAS
1257-78-9
58-38-8
84-02-6
88021-18-5
2930627-64-6
Tags
natural product
drug
available
Approved by
FDA
First approval
1957
1956
Drug Status
approved
vet_approved
Drug indication
Anti-Emetic
Anti-Emetic,Anti-Emetic
Nausea
Antipsychotic,Antipsychotic
Antipsychotic
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS Prochlorperazine is an antipsychotic agent that works to promote postsynaptic inhibition of dopaminergic neurons.[L6640] It also exerts its anti-emetic actions via anti-dopaminergic effects, where it displays similar efficacy as ondansteron, a 5HT-3 receptor antagonist and anti-emetic, in preventing delayed nausea and vomiting.[A179179] Prochlorperazine was shown to inhibit histaminergic, cholinergic and alpha-1 adrenergic receptors.[A179173,L6637] The blockade of alpha-1 adrenergic receptors may result in sedation, muscle relaxation, and hypotension. It displays anti-anxiety effects as well.[L6640] Compared to other phenothiazine derivatives, prochlorperazine is less sedating and has a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics.[L6646] Other than its primary action on D2 receptors, one study showed that prochlorperazine may inhibit the P2X7 receptor in human macrophages, leading to inhibition of calcium ion influx.[L6637]
MOA The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its anti-dopaminergic effects. Prochlorperazine blocks the D2 dopamine receptors in the brain, which are somatodendritic autoreceptors. Inhibition of D2 receptor signaling results in the blockade of postsynaptic dopamine receptors in the mesolimbic system [L6643] and an increased dopamine turnover. Nausea and vomiting are proposed to arise from peripheral or central stimulation of serotonin type 3 (5-HT3) and dopamine type 2 receptors, the predominant receptors expressed at the chemoreceptor trigger zone (CTZ).[A179194,L6643] Prochlorperazine exerts antiemetic effects and was shown to inhibit apomorphine-induced vomiting by blocking D2 dopamine receptors in the CTZ.[A179179].
INDICATION Indicated for the symptomatic treatment of severe nausea and vomiting.[label]; ; Indicated for the management of manifestations of psychotic disorders, such as schizophrenia and generalized non-psychotic anxiety. The use of prochlorperazine for the management of generalized non-psychotic anxiety is typically not a first-line therapy and should be limited to doses of less than 20 mg per day or for shorter than 12 weeks.[label,L6634]; ; Off-label uses include use in emergency settings for adult and pediatric migraines. The American Headache Society recommends the use of prochlorperazine as the first-line medication in this setting. In pediatric migraines, a non-steroidal anti-inflammatory agent is often used in combination with dopamine antagonist.[L6637]
ROE Prochlorperazine is reported to be mainly excreted via the feces and bile.[L6646] Low quantities of unchanged prochlorperazine and its metabolite were detectable in the urine.[A179173]
METABOLISM Prochlorperazine undergoes hepatic metabolism involving oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid.[L6649] The oxidation reaction is mediated by CYP2D6.[A179179] N-desmethyl prochlorperazine was detected in the plasma[A179173], as well as prochlorperazine sulfoxide, prochlorperazine 7-hydroxide and prochlorperazine sulfoxide 4'-N-oxide, following oral and buccal administration.[A179188] Prochlorperazine may enter the enterohepatic circulation.[L6646]
ABSORPTION Following oral administration, prochlorperazine is reported to be well absorbed from the gastrointestinal tract. The onset of pharmacological action is about 30 to 40 minutes following oral administration and 10 to 20 minutes following intramuscular administration. The duration of action for all routes is about 3 to 4 hours.[L6646] Following oral administration in healthy volunteers, the mean oral bioavailability was about 12.5%. In these patients, the time to reach the peak plasma concentrations was about 5 hours. Repeated oral dosing resulted in an accumulation of prochlorperazine and its metabolite. Following multiple twice daily dosing, the steady state of prochlorperazine was reached by 7 days.[A179173]
HALF-LIFE Following intravenous and single oral dose administration, the terminal elimination half live were 9 and 8 hours, respectively.[A179173]
DESCRIPTION Prochlorperazine is a potent phenothiazine neuroleptic. (GtoPdb)
DESCRIPTION inhibitor of dopamine receptor D2 (Informer Set)
DESCRIPTION D2 receptor antagonist. Also 5-HT3 and nAChR antagonist (Tocriscreen Plus)
DESCRIPTION Prochlorperazine is a dopamine D2 receptor antagonist. It belongs to the phenothiazine class of antipsychotic agents and can be used for the antiemetic treatment of nausea and vertigo. Prochlorperazine is also used to treat migraine headaches. (BOC Sciences Bioactive Compounds)
DESCRIPTION Antipsychotic agent; used in the treatment of spastic gastrointestinal disorders (LOPAC library)
Cell lines
1
Organisms
2
Compound Sets
33
AdooQ Bioactive Compound Library
A16172
BOC Sciences Bioactive Compounds
prochlorperazine-dimaleate-cas-84-02-6-item-78216
Cayman Chemical Bioactives
20742
31916
ChEMBL Approved Drugs
CHEMBL728
CHEMBL1201154
CHEMBL1314751
ChEMBL Drugs
CHEMBL728
CHEMBL1201154
CHEMBL1314751
Concise Guide to Pharmacology 2017/18
7279
Concise Guide to Pharmacology 2019/20
7279
Concise Guide to Pharmacology 2021/22
7279
Concise Guide to Pharmacology 2023/24
7279
Drug Repurposing Hub
DrugBank
DB00433
DrugBank Approved Drugs
DB00433
DrugCentral
2274
DrugCentral Approved Drugs
2274
DrugMAP
DM53SRA
DrugMAP Approved Drugs
DM53SRA
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
7279
Informer Set
33166
Ki Database
PROCHLORPERAZINE
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL728
NCATS Inxight Approved Drugs
YHP6YLT61T
NIH Clinical Collections (NCC)
NPC Screening Collection
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
prochlorperazine
TargetMol Bioactive Compound Library
T0385
The Spectrum Collection
Tocriscreen Plus
3287
External IDs
89
Properties
(calculated by RDKit )
Molecular Weight
373.14
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
0
Rotatable Bonds
4
Ring Count
4
Aromatic Ring Count
2
cLogP
4.58
TPSA
9.72
Fraction CSP3
0.4
Chiral centers
0.0
Largest ring
6.0
QED
0.78
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
DRD2
Dopamine Receptor
D2
DRD1, DRD2, DRD3, DRD4
Compound status
FDA
Target Type
7-TM Receptors
Pathway
GPCR/G protein
Neuronal Signaling
Neuroscience
Indication
nausea, vomiting
MOA
Dopamine Receptor antagonist
Therapeutic Class
Antipsychotic Agents
Solubility
DMSO (Slightly)
Source data