General
Preferred name
OLANZAPINE
Synonyms
LY170053 ()
Zyprexa ()
LY170053,Zyprexa, Zalasta, Zolafren, Olzapin, Oferta, Zypadhera ()
Olanzapine-d8 ()
Olanzapine apotex ()
Olanzapine mylan ()
Olansek ()
Zyprexa velotab ()
Zyprexa Zydis ()
Olazax ()
LY-170053 ()
Zalasta ()
Arkolamyl ()
Olanzapine glenmark ()
Olanzapine teva ()
Olanzapine cipla ()
Olazax disperzi ()
Olanzapine embonate ()
Zyprexa Relprevv ()
Zypadhera ()
Olanzapine (as embonate) ()
Olanzapine pamoate monohydrate ()
Olanzapine pamoate anhydrous ()
OLANZAPINE PAMOATE ()
P&D ID
PD000646
CAS
132539-06-1
1093380-13-2
Tags
available
natural product
drug
Approved by
FDA
EMA
First approval
1996
2009
Drug indication
Schizophrenia
Antipsychotic
Drug Status
investigational
withdrawn
approved
Max Phase
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE Olanzapine presents a half-life ranging between 21 to 54 hours with an average half-life of 30 hours.[A177014]
PHARMACODYNAMICS The effect of olanzapine in the D2 receptor is reported to produce the positive effects of this drug such as a decrease in hallucinations, delusions, disorganized speech, disorganized thought, and disorganized behavior. On the other hand, its effect on the serotonin 5HT2A receptor prevents the onset of anhedonia, flat affect, alogia, avolition and poor attention.[A177014] Based on the specific mechanism of action, olanzapine presents a higher affinity for the dopamine D2 receptor when compared to the rest of the dopamine receptor isotypes. This characteristic significantly reduces the presence of side effects.[T554]; ; Clinical trials for the original use of olanzapine demonstrated significant effectiveness in the treatment of schizophrenia and bipolar disorder in adults and acute manic or mixed episodes associated with bipolar disorder in adolescents.[A177008]; ; The effect of olanzapine on dopamine and serotonin receptors has been suggested to reduce chemotherapy-induced nausea and vomiting as those receptors are suggested to be involved in this process. For this effect, several clinical trials have been conducted and it has been shown that olanzapine can produce a significant increase in total control of nausea and vomiting.[A176993] In a high-level study of the effect of olanzapine for this condition, a complete response on the delay phase was observed in 84% of the individual and control of emesis of over 80% despite the phase.[A176999]
ROE Olanzapine is mainly eliminated through metabolism and hence, only 7% of the eliminated drug can be found as the unchanged form. It is mainly excreted in the urine which represents around 53% of the excreted dose followed by the feces that represent about 30%.[A177014]
MOA The activity of olanzapine is achieved by the antagonism of multiple neuronal receptors including the dopamine receptor D1, D2, D3 and D4 in the brain, the serotonin receptors 5HT2A, 5HT2C, 5HT3 and 5HT6, the alpha-1 adrenergic receptor, the histamine receptor H1 and multiple muscarinic receptors.[A176993, A176999]; ; As abovementioned, olanzapine presents a wide profile of targets, however, its antagonistic effect towards the dopamine D2 receptor in the mesolimbic pathway is key as it blocks dopamine from having a potential action at the post-synaptic receptor. The binding of olanzapine to the dopamine D2 receptors is easily dissociable and hence, it allows for a certain degree of dopamine neurotransmission.[A177014]; ; On the other hand, olanzapine acts in the serotonin 5HT2A receptors in the frontal cortex in a similar manner than the reported on dopamine D2 receptors. This determined effect allows for a decrease in adverse effects.[A177014]
TOXICITY The toxicity symptoms of olanzapine are known to include somnolence, mydriasis, blurred vision, respiratory depression, hypotension, extrapyramidal symptoms and anticholinergic effects. The overdosage effects in children are generally associated with more significant side effects.[A177059]; ; The maximum registered dosage of olanzapine in clinical trials was of 300 mg and it was reported to present drowsiness and slurred speech. However, on post-marketing surveillance, a wide range of symptoms have been presented including agitation, dysarthria, tachycardia, extrapyramidal symptoms, and reduced consciousness. One case of overdosage-driven death was reported after ingestion of 450 mg of olanzapine. In the cases of acute overdosage, the establishment of adequate oxygenation and ventilation, gastric lavage and administration of activated charcoal with a laxative is recommended.[FDA label]; ; In carcinogenesis studies, olanzapine was showed to present an increase in the incidence of liver hemangiomas and hemangiosarcomas as well as mammary gland adenomas, and adenocarcinomas. On fertility studies, there was solely found impairment in male mating performance and delays in ovulation. There is no evidence of mutagenic, genotoxic potential not adverse events on fertility.[FDA label]
ABSORPTION Olanzapine presents a linear pharmacokinetic profile and, after daily administration, it reaches steady-state in about a week.[A177014] Under the administration of a normal dosage of olanzapine, the steady-state plasma concentration does not seem to exceed 150 ng/ml with an AUC of 333 ng/h/ml.[A177059, T554]; ; The absorption of olanzapine is not affected by the concomitant administration of food. The pharmacokinetic profile of olanzapine is characterized by reaching peak plasma concentration of 156.9 ng/ml approximately 6 hours after oral administration.[T548]
INDICATION Olanzapine was initially used orally and intramuscularly for the chronic treatment of schizophrenia in patients over 13 years old and other psychiatric disorders such as bipolar I disorder including mixed or manic episodes.[A177014] ; ; Olanzapine is also indicated, in combination with lithium or valproate for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in adults.[FDA label]; ; As well, olanzapine is indicated, in combination with fluoxetine for the treatment of episodes of depression associated with bipolar disorder type 1 and treatment-resistant depression in patients over 10 years old.[A177014]; ; Olanzapine is also approved for the management of psychomotor agitation associated with schizophrenia and bipolar I mania.[FDA label]; ; Schizophrenia is a complex biochemical brain disorder that affects the person's ability to differentiate reality. It is usually observed as the presence of delusions, hallucinations, social withdrawal and disturbed thinking.[L5936]; ; Bipolar disorder is a mental health condition defined by periods of extreme mood disturbances. It is categorized in different types from which type 1 is known to involve episodes of severe mania and often depression while type 2 presents less severe forms of mania.[L5939]
METABOLISM Olanzapine is greatly metabolized in the liver, which represents around 40% of the administered dose, mainly by the activity of glucuronide enzymes and by the cytochrome P450 system. From the CYP system, the main metabolic enzymes are CYP1A2 and CYP2D6.[A177014] As part of the phase I metabolism, the major circulating metabolites of olanzapine, accounting for approximate 50-60% of this phase, are the 10-N-glucuronide and the 4'-N-desmethyl olanzapine which are clinically inactive and formed by the activity of CYP1A2.[T548] On the other hand, CYP2D6 catalyzes the formation of 2-OH olanzapine and the flavin-containing monooxygenase (FMO3) is responsible for N-oxide olanzapine.[T551]; ; On the phase II metabolism of olanzapine, UGT1A4 is the key player by generating direct conjugation forms of olanzapine.[T551]
DESCRIPTION Potent S1P1 receptor agonist (Tocris Bioactive Compound Library)
DESCRIPTION 5-HT2A/D2 antagonist; atypical antipsychotic (Tocriscreen Plus)
Cell lines
0
Organisms
1
Compound Sets
32
Axon Medchem Screening Library
1298
Cayman Chemical Bioactives
11937
25447
ChEMBL Approved Drugs
CHEMBL715
CHEMBL3989694
ChEMBL Drugs
CHEMBL715
CHEMBL3989694
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB00334
DrugBank Approved Drugs
DB00334
DrugCentral
1982
DrugCentral Approved Drugs
1982
DrugMAP
DMPFN6Y
DrugMAP Approved Drugs
DMPFN6Y
DrugMatrix
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS100696
JUMP-Target 1 Compound Set
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL715
MedChem Express Bioactive Compound Library
HY-14541
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
N7U69T4SZR
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Olanzapine(Zyprexa)
TargetMol Bioactive Compound Library
T1567
The Spectrum Collection
Tocris Bioactive Compound Library
4349
Tocriscreen Plus
4349
Withdrawn 2.0
EMA30
External IDs
70
Properties
(calculated by RDKit )
Molecular Weight
312.14
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
1
Rotatable Bonds
0
Ring Count
4
Aromatic Ring Count
2
cLogP
3.44
TPSA
30.87
Fraction CSP3
0.35
Chiral centers
0.0
Largest ring
7.0
QED
0.81
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
Neuroscience
GPCR/G protein
Apoptosis
Autophagy
Neuronal Signaling
Target
5-HT
HT
mAChR
Adrenergic Receptor
dopamine
ADRA1A, ADRA1B, ADRA2A, ADRA2B, ADRA2C, ADRB1, ADRB2, ADRB3, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, DRD1, DRD2, DRD3, DRD4, DRD5, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, HRH1, HRH2, HRH4, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR3A, HTR5A, HTR6, HTR7
Atypical antipsychotic
CHRM2
5-HT Receptor
Dopamine Receptor
Mitophagy
5-HT Receptor,Dopamine Receptor
Primary Target
5-HT2A Receptors
MOA
5-HT Receptor antagonist
AChR antagonist
Adrenergic Receptor antagonist
Antagonist
Dopamine D2 Antagonists
5-HT2A Inverse Agonist
ADRA1B gene inhibitor
dopamine receptor antagonist, serotonin receptor antagonist
Member status
virtual
Indication
schizophrenia, bipolar disorder
ATC
N05AH03
Therapeutic Indication
Neuroleptic
Therapeutic Class
CNS & PNS
Antipsychotic Agents
Source data