General
Preferred name
ARIPIPRAZOLE LAUROXIL
Synonyms
Aristada initio ()
ALKS-9072 ()
Aristada initio kit ()
Aristada ()
ALKS-9070 ()
ALKS 9072 ()
RDC-3317 ()
RDC3317 ()
P&D ID
PD073693
CAS
1259305-29-7
Tags
available
prodrug
drug
Approved by
FDA
First approval
2015
Drug Status
investigational
approved
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)
TOXICITY LD50 in rat following intramuscular injection was >60 mg aripiprazole equivalents [MSDS]. Oral LD50 of aripiprazole in female rat, male rat, and monkey were 705 mg/kg, 965 mg/kg, and >2000 mg/kg, respectively [MSDS]. Most common adverse reaction of aripiprazole was akathisia. A case of drug overdosage occurred followinga acute ingestion of 1260 mg aripiprazole, which is approximately 42 times the maximum recommended daily dose. Overdose was associated with vomiting, somnolence, and tremor [FDA Label]. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia [FDA Label].; ; Aripiprazole is an antipsychotic drug that may develop Neuroleptic Malignant Syndrome (NMS), which is manifested with hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. In case of NMS, aripiprazole should be discontinued immediately, and intensive symptomatic treatment and medical monitoring should be initiated [FDA Label].
MOA The pharmacological activity of aripiprazole lauroxil is thought to be mainly mediated by its metabolite aripiprazole, and to a lesser extent, dehydro-aripiprazole. Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at the serotonin 5-HT2A receptor [FDA Label]. The desired outcome of antipsuchotic agents in schizophrenia is to inhibit dopaminergic transmission in the limbic system and enhance dopaminergic transmission in the prefrontal cortex. As a partial agonist at D2 receptors in the mesolimbic dopaminergic pathway, aripiprazole acts as a functional antagonist in the mesolimbic dopamine pathway and reduces the extent of dopaminergic pathway activity. This results in reduced positive symptoms in schizophrenia and extrapyramidal motor side effects [A34403]. In contrast, aripiprazole is thought to act as a functional agonist in the mesocortical pathway, where reduced dopamine activity is seen in association with negative symptoms and cognitive impairment [A34403]. Antagonism at 5-HT2A receptors by aripiprazole alleviates the negative symptoms and cognitive impairment of schizophrenia [T28]. 5-HT2A receptors are Gi/Go-coupled that upon activation, produce neuronal inhibition via decreased neuronal excitability and decreased transmitter release at the nerve terminals. In the nigrostriatal pathway, 5-HT2A regulates the release of dopamine. Through antagonism of 5-HT2A receptors, aripiprazole disinhibits the release of dopamine in the striatum and enhance the levels of the transmitters at the nerve terminals [T28]. The combined effects of D2 and 5-HT2A antagonism are thought to counteract the increased dopamine function causing increased extrapyramidal side effects [T28]. Blocking 5-HT2A receptors may also lead to the modulation of glutamate release in the mesocortical circuit, which is a transmitter that plays a role in schizophrenia [A34403]. 5-HT1A receptors are autoreceptors that inhibit 5-HT release upon activation. Aripiprazole is a partial agonist at theses receptors and reduces 5-HT release; this results in potentiated dopamine release in the striatum and prefrontal cortex [T28]. It is reported that therapeutic doses of aripiprazole occupies up to 90% of brain D2 receptors in a dose-dependent manner [A4965]. ; ; Apripiprazole targets different receptors that lead to drug-related adverse reactions; for example, the antagonist activity at the alpha-1 adrenergic receptors results in orthostatic hypotension [A34289]. Aripiprazole's antagonism of histamine H1 receptors may explain the somnolence observed with this drug [A34289].
Compound Sets
9
ChEMBL Approved Drugs
CHEMBL2219425
ChEMBL Drugs
CHEMBL2219425
Drug Repurposing Hub
DrugBank
DB14185
DrugBank Approved Drugs
DB14185
DrugCentral
5052
DrugCentral Approved Drugs
5052
MedChem Express Bioactive Compound Library
HY-108751
ReFrame library
External IDs
27
Properties
(calculated by RDKit )
Molecular Weight
659.33
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
0
Rotatable Bonds
19
Ring Count
4
Aromatic Ring Count
2
cLogP
8.68
TPSA
62.32
Fraction CSP3
0.61
Chiral centers
0.0
Largest ring
6.0
QED
0.11
Structural alerts
0
No structural alerts detected
Custom attributes
(extracted from source data)
Indication
schizophrenia
MOA
serotonin receptor agonist
Source data