PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
olanzapine

2D structure

Overview

Generic Names: olanzapine
Trade Names: Olansek; Symbyax; Zydis; Zyprexa; Zyprexa Intramuscular; Zyprexa Zydis
PharmGKB Accession Id: PA450688

Description

Olanzapine is an atypical antipsychotic, approved by the FDA in 1996. Olanzapine is manufactured and marketed by the pharmaceutical company Eli Lilly and Company, whose patent for olanzapine proper ends in 2011. (source: Drug Bank)

Indication

For the treatment of schizophrenia and manic depression (bipolar disorder). (source: Drug Bank)

ATC Therapeutic Category

  • N05AH:Diazepines, oxazepines and thiazepines

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Olanzapine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Olanzapine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT<sub>2</sub> receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Olanzapine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with olanzapine. (source: Drug Bank)

Pharmacology

Olanzapine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, olanzapine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT<sub>2</sub>) receptors. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (source: Drug Bank)

Protein Binding

93% (source: Drug Bank)

Absorption

Well absorbed, with approximately 40% of the dose metabolized before reaching the systemic circulation. (source: Drug Bank)

Toxicity

Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness and coma. Death has been reported after an acute overdose of 0.45g, but also survival after an acute overdose of 1500g. (source: Drug Bank)

Isomeric SMILES Code:

Cc1cc2c(s1)Nc3ccccc3N=C2N4CCN(CC4)C (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs4606 at chr1:191047795 in RGS2
    This variant is located in the 3'-regulatory region of RGS2, and is known to influence RGS2 mRNA levels and protein expression. It has been shown to be associated antipsychotic-induced parkinsonism (AIP) with possible protective effect of the minor G allele of rs4606.
    Related Drugs:
    clozapine, olanzapine, risperidone
    Related Diseases:
    Parkinson Disease, Psychotic Disorders
    Evidence:
    PMID:18347610
  2. rs6280 at chr3:115373505 in DRD3
    A study on 88 olanzapine-treated patients with schizophrenia found that the Gly/gly genotype was significantly associated with greater positive symptom improvement.
    Variant Name:
    DRD3: 9 Ser>Gly
    Related Drugs:
    olanzapine
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:18320559
  3. rs1045642 at chr7:86976581 in ABCB1
    Risk or phenotype-associated allele: T. Phenotype: In subjects carrying one or two T alleles of this variant, the plasma olanzapine level alone was positively associated with percent change in Brief Psychiatric Rating Scale (BPRS) score. As olanzapine plasma levels increased, the BPRS score increased. Study size: 41. Study population/ethnicity: Patients with schizophrenia; > 90% Caucasian. Significance metric(s): p = 0.02. Type of association: CO.
    Variant Name:
    PGP C3435T; ABCB1:3435C>T
    Related Drugs:
    olanzapine
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:17038883
  4. rs4731426 at chr7:127669306 in LEP
    This intronic variant is moderately associated with olanzapine-induced median weight gain and significantly associated with extreme weight gain in schizophrenia subjects from north India.This variant alters the binding of a transcription factor (zinc finger 5) using in silico analysis.
    Related Drugs:
    olanzapine
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:18681781
  5. rs4994 at chr8:37942955 in ADRB3
    Arg in position 64 associated with olanzapine-induced weight gain
    Variant Name:
    ADRB3:Trp64Arg
    Related Drugs:
    olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:19193342
  6. rs2228622 at chr9:4554432 in SLC1A1
    Risk or phenotype-associated variant: A. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.
    Variant Name:
    SLC1A1:rs2228622G>A, SNP2, Exon 4(syn)
    Related Drugs:
    clozapine, olanzapine, risperidone
    Related Diseases:
    Obsessive-Compulsive Disorder, Schizophrenia
    Evidence:
    PMID:19884611
  7. rs3780413 at chr9:4557353 in SLC1A1
    Risk or phenotype-associated variant: C. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.
    Variant Name:
    SLC1A1:rss3780413C>G, SNP3, Intron 5
    Related Drugs:
    clozapine, olanzapine, risperidone
    Related Diseases:
    Obsessive-Compulsive Disorder, Schizophrenia
    Evidence:
    PMID:19884611
  8. rs3780412 at chr9:4562480 in SLC1A1
    Risk or phenotype-associated variant: G. Phenotype: The A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with atypical antipsychotic-induced obsessive compulsive symptoms. Study size: 94. Study population/ethnicity: Patients with schizophrenia receiving atypical antipsychotics; Asian; Korea. Significance metric(s): p = 0.04. Type of association: CO.
    Variant Name:
    SLC1A1:rs3780412A>G, SNP4, Intron 7
    Related Drugs:
    clozapine, olanzapine, risperidone
    Related Diseases:
    Obsessive-Compulsive Disorder, Schizophrenia
    Evidence:
    PMID:19884611
  9. rs1800497 at chr11:112776038 in ANKK1
    Risk or phenotype-associated allele: T. Phenotype: In the combined medication group patients with the A1 (T) allele had 40% higher prolactin levels than patients without this allele. Study size: 144 schizophrenic patients. Study population: White patients.
    Variant Name:
    Taq1A (32806C>T)
    Related Drugs:
    antipsychotics, clozapine, olanzapine, risperidone
    Related Diseases:
    Hyperprolactinemia
    Evidence:
    PMID:15286066
  10. rs1800497 at chr11:112776038 in ANKK1
    Risk or phenotype-associated allele: T. Phenotype: The T allele was associated with weight gain of at least 7% in schizophrenia patients treatment with clozapine or olanzapine. Study size: 206. Study population/ethnicity: European american; German; Schizophrenia. Significance metric(s): OR = 2.18 (CI: 1.00-4.75). Type of association: PD.
    Variant Name:
    TaqIA
    Related Drugs:
    antipsychotics, clozapine, olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:20714340
  11. rs6277 at chr11:112788669 in DRD2
    Risk or phenotype-associated allele: CC. Phenotype: The CC genotype was associated with weight gain of at least 7% in schizophrenia patients treatment with clozapine or olanzapine. Study size: 206. Study population/ethnicity: European american; African American; German; Schizophrenia. Significance metric(s): OR = 3.37 (CI = 1.00-11.36). Type of association: PD.
    Variant Name:
    C957T
    Related Drugs:
    antipsychotics, clozapine, olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:20714340
  12. rs1079598 at chr11:112801484 in DRD2
    Risk or phenotype-associated allele: C. Phenotype: The C allele was associated with weight gain of at least 7% in schizophrenia patients treatment with clozapine or olanzapine. Study size: 206. Study population/ethnicity: European american; African American; German; Schizophrenia. Significance metric(s): OR = 3.44 (CI: 1.46-8.11). Type of association: PD.
    Related Drugs:
    antipsychotics, clozapine, olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:20714340
  13. rs1799732 at chr11:112851462 in DRD2
    Risk or phenotype-associated allele: Del. Phenotype: Carriers of the -141C Del allele showed significantly longer time to respond to the antipsychotics relative to the Ins/Ins homozygous patients (p<0.03). Study size: 61 patients experiencing their first episode of schizophrenia. Study population: 41% African American; 28% Caucasian (European); 18% Hispanic; 5% Asian; 8% other.
    Variant Name:
    DRD2: -141C Ins/Del
    Related Drugs:
    olanzapine, risperidone
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:16513877
  14. rs1799732 at chr11:112851462 in DRD2
    Phenotype: Results of this meta-analysis showed that the group of Del allele carrier was significantly associated with poorer antipsychotic drug response relative to the Ins/Ins genotype. Study size: meta-analysis included six individual studies, 687 patients total.
    Variant Name:
    DRD2: -141C Ins/Del
    Related Drugs:
    aripiprazole, chlorpromazine, clozapine, olanzapine, risperidone
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:20194480
  15. rs5443 at chr12:6825136 in GNB3, USP5
    T allele is associated with olanzapine-induced weight gain
    Variant Name:
    GNB3:825C>T
    Related Drugs:
    olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:19193342
  16. rs7997012 at chr13:46309986 in HTR2A
    Risk or phenotype-associated allele: A. Phenotype: Patients with the 5-HTR2A intron 2 (rs7997012) AA genotype suffered from more pronounced side effects compared to carriers of the GA or GG genotype. Study size: 124. Study population/ethnicity: Caucasian; Patients with psychiatric disorders. Significance metric(s): p = 0.018 and p = 0.002. Type of association: PD.
    Variant Name:
    5-HTR2A intron 2 variant
    Related Drugs:
    olanzapine
    Evidence:
    PMID:19636338
  17. rs6313 at chr13:46367941 in HTR2A
    T allele is associated with olanzapine-induced weight gain
    Variant Name:
    HTR2A:T102C; HTR2A:102C>T
    Related Drugs:
    olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:19193342
  18. rs6313 at chr13:46367941 in HTR2A
    Risk or phenotype-associated allele (s): T/T. Phenotype: Patients, with a diagnosis of probable Alzheimer's disease, carrying the TT genotype were the most delusional during the follow-up period of a study evaluating the association of HTR2A 102T/C polymorphism with psychotic symptom severity. Patients with delusion symptoms carrying the CT and TT genotypes were resistant to the treatment with antipsychotic drugs. Study size: 80. Study population/ethnicity: Caucasian
    Variant Name:
    HTR2A:T102C; HTR2A:102C>T
    Related Drugs:
    olanzapine, risperidone
    Related Diseases:
    Alzheimer Disease
    Evidence:
    PMID:19494443
  19. rs762551 at chr15:72828970 in CYP1A2
    Risk or phenotype-associated allele: A. Phenotype: CYP1A2*1F/*1F genotype was associated with reduced dose-/body weight-normalized olanzapine serum concentrations compared to homo- and heterozygote carriers of CYP1A2*1A. Study size: 124. Study population/ethnicity: Caucasian; Patients with psychiatric disorders.Type of association: PD.
    Variant Name:
    CYP1A2*1F; CYP1A2:(-163)C>A
    Related Drugs:
    olanzapine
    Evidence:
    PMID:19636338
  20. rs3813929 at chrX:113724776 in HTR2C
    This variant is associated with Olanzapine-induced weight gain. The -759T allele confers protective effect towards Olanzapine-induced weight gain in a study consisting of 107 patients with schizophrenia.
    Variant Name:
    HTR2C: -759C/T
    Related Drugs:
    olanzapine
    Related Diseases:
    Schizophrenia, Weight gain
    Evidence:
    PMID:19622037
  21. rs3813929 at chrX:113724776 in HTR2C
    Risk or phenotype-associated allele: T. Phenotype: The T allele was more frequently found in subjects not gaining 10% or more of their body weight, compared with those who did gain 10% or more of their body weight. None of the subjects who gained >10% of their initial body weight over 6 weeks carried a T allele (0/11). Study size: 42. Study population/ethnicity: Caucasian acutely ill patients with schizophrenia taking olanzapine. Significance metric(s): p = 0.0035. Type of association: CO.
    Variant Name:
    HTR2C:-759C/T; HTR2C:-759C>T
    Related Drugs:
    olanzapine
    Related Diseases:
    Schizophrenia
    Evidence:
    PMID:15666332
  22. rs3813929 at chrX:113724776 in HTR2C
    Risk or phenotype-associated allele: T. Phenotype: Short-term weight gain under olanzapine therapy was significantly lower for 5-HTR2C -759 T-allele carriers. Study size: 124. Study population/ethnicity: Caucasian; Patients with psychiatric disorders. Significance metric(s): p = 0.011. Type of association: PK.
    Variant Name:
    HTR2C: -759C/T; HTR2C:(-759)C>T
    Related Drugs:
    olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:19636338
  23. rs518147 at chrX:113724838 in HTR2C
    This variant is associated with Olanzapine-induced weight gain. The -697C allele confers protective effect towards Olanzapine-induced weight gain in a study consisting of 107 patients with schizophrenia.
    Variant Name:
    HTR2C: -697G/C
    Related Drugs:
    olanzapine
    Related Diseases:
    Schizophrenia, Weight gain
    Evidence:
    PMID:19622037
  24. rs6318 at chrX:113871991 in HTR2C
    Ser in position 23 is associated with olanzapine-induced weight gain
    Variant Name:
    HTR2C:23Ser; HTR2C:Cys23Ser
    Related Drugs:
    olanzapine
    Related Diseases:
    Weight gain
    Evidence:
    PMID:19193342
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
ADRA2A
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ADRB3
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
ANKK1
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
APOA4
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
APOA5
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
APOC3
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
APOE
  •   
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
COMT
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  • PD
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  • CO
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
DRD1
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Has annotations
DRD2
  •   
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
DRD3
  •   
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
DRD4
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
DRD5
  •   
  • PD
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
GNB3
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
GRM3
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
HRH1
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
HTR2A
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
HTR2C
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
KCNH2
  •   
  • PD
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
LEP
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
Phenotype data available No genotype data Literature annotations available Not annotated
LPL
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
MCHR1
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
PRKCB
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
RGS2
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
SCARB1
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC1A1
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
UGT1A4
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available No literature annotations Not annotated
USP5
  •   
  •   
  •   
  •   
  •   
Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
HTR2A Uncurated Annotation (source: Drug Bank)
HTR2C Uncurated Annotation (source: Drug Bank)
ADRA1B Uncurated Annotation (source: Drug Bank)
CHRM1 Uncurated Annotation (source: Drug Bank)
CHRM2 Uncurated Annotation (source: Drug Bank)
CHRM3 Uncurated Annotation (source: Drug Bank)
CHRM4 Uncurated Annotation (source: Drug Bank)
CHRM5 Uncurated Annotation (source: Drug Bank)
DRD1 Uncurated Annotation (source: Drug Bank)
DRD2 Uncurated Annotation (source: Drug Bank)
DRD3 Uncurated Annotation (source: Drug Bank)
DRD4 Uncurated Annotation (source: Drug Bank)
HRH1 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
donepezil Uncurated Annotation Possible antagonism of action (source: Drug Bank)
fluvoxamine Uncurated Annotation Fluvoxamine increases the effect and toxicity of olanzapine (source: Drug Bank)
galantamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
ritonavir Uncurated Annotation Ritonavir decreases the effect of olanzapine (source: Drug Bank)
rivastigmine Uncurated Annotation Possible antagonism of action (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Body Weight Changes
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Hyperlipidemias
  •   
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Metabolic Diseases
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Metabolic Syndrome X
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Obsessive-Compulsive Disorder
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Parkinson Disease
  •   
  • PD
  •   
  •   
  •   
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Psychotic Disorders
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Schizophrenia
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
tardive dyskinesia
  •   
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Weight gain
  • CO
  • PD
  •   
  • FA
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00334
KEGG Compound ID:
C07322
KEGG Drug ID:
D00454
PubChem Compound ID:
4585
PubChem Substance ID:
197059
IUPHAR Ligand ID:
47

Common Searches

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Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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