| Candidate ID: | R0119 |
| Source ID: | DB00334 |
| Source Type: | approved; investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Olanzapine
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| Synonyms: |
2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine; Olanzapin
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| Molecular Formula: |
C17H20N4S
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| SMILES: |
CN1CCN(CC1)C1=NC2=CC=CC=C2NC2=C1C=C(C)S2
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| Structure: |
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| DrugBank Description: |
Olanzapine is a thienobenzodiazepine classified as an atypical or second-generation antipsychotic agent. The second-generation antipsychotics were introduced in the 90s and quickly gained traction due to their impressive efficacy, reduced risk for extrapyramidal side effects and reduced susceptibility to drug-drug interactions. Olanzapine very closely resembles and only differs by two additional methyl groups and the absence of a chloride moiety. It was discovered by scientists at Eli Lilly and approved to be marketed in the US in 1996.
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| CAS Number: |
132539-06-1
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| Molecular Weight: |
312.432
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| DrugBank 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.
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.
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.
Olanzapine is also approved for the management of psychomotor agitation associated with schizophrenia and bipolar I mania.
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.
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.
Olanzapine is also indicated in combination with for the treatment of bipolar I disorder, either as an adjunct to lithium or valproate or as monotherapy for the acute treatment of manic or mixed episodes or as maintenance therapy, and for the treatment of schizophrenia in adults.
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| DrugBank Pharmacology: |
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. 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.
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.
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. 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.
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| DrugBank 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.
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.
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.
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| Targets: |
5-hydroxytryptamine receptor 2A antagonist; Dopamine D2 receptor antagonist; Dopamine D1 receptor antagonist; Dopamine D5 receptor antagonist; Dopamine D3 receptor antagonist; Dopamine D4 receptor antagonist; 5-hydroxytryptamine receptor 2C antagonist; 5-hydroxytryptamine receptor 3A antagonist; 5-hydroxytryptamine receptor 6 antagonist; Histamine H1 receptor antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; D(1) dopamine receptor antagonist; Beta adrenergic receptor inhibitor; 5-hydroxytryptamine receptor 1 inhibitor; GABA(A) Receptor Benzodiazepine Binding Site inhibitor
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| Inclusion Criteria: |
Indication associated
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