From the Guidelines
Olanzapine works by blocking dopamine D2 receptors in the brain, with a complex mechanism of action involving antagonism at multiple neurotransmitter receptors, including serotonin, histamine, muscarinic, and alpha-1 adrenergic receptors, in addition to dopamine receptors 1. The relationship between olanzapine and dopamine is characterized by olanzapine's ability to block dopamine receptors, specifically D1, D2, D3, and D4, with its greatest affinity for D2 and D4 1.
Key Points
- Olanzapine has a looser binding profile compared to typical antipsychotics, which preferentially affects the mesolimbic dopamine pathway rather than the nigrostriatal pathway 1.
- This selective action helps reduce positive symptoms of psychosis, such as hallucinations and delusions, by decreasing dopamine activity in the mesolimbic pathway while causing fewer extrapyramidal side effects than typical antipsychotics 1.
- Olanzapine's lower occupancy of D2 receptors (65-80% compared to >90% with typical antipsychotics) and its faster dissociation rate from these receptors also contribute to its improved side effect profile while maintaining therapeutic efficacy 1.
Mechanism of Action
Olanzapine's mechanism of action involves antagonism at multiple neurotransmitter receptors, including:
- Serotonin (5-HT2A, 5-HT2C)
- Histamine (H1)
- Muscarinic (M1-M5)
- Alpha-1 adrenergic receptors
- Dopamine receptors (D1, D2, D3, D4) This complex mechanism of action contributes to olanzapine's therapeutic efficacy and improved side effect profile compared to typical antipsychotics 1.
Clinical Implications
The use of olanzapine in clinical practice is supported by its efficacy in reducing positive symptoms of psychosis and its improved side effect profile compared to typical antipsychotics 1.
Dosage
Examples of appropriate initial target doses for most patients are risperidone 2 mg/day or olanzapine 7.5–10.0 mg/day 1. It is essential to consider the individual patient's needs and adjust the dosage accordingly to minimize the risk of adverse effects while maintaining therapeutic efficacy 1.
From the FDA Drug Label
The mechanism of action of olanzapine, in the listed indications is unclear. However, the efficacy of olanzapine in schizophrenia could be mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism. Olanzapine binds with high affinity to the following receptors: serotonin 5HT2A/2C, 5HT6 (Ki=4,11, and 5 nM, respectively), dopamine D1-4 (Ki=11-31 nM), histamine H1 (Ki=7 nM), and adrenergic α1 receptors (Ki=19 nM).
The relationship between Olanzapine and dopamine is that olanzapine is a dopamine antagonist, specifically binding to dopamine D1-4 receptors with high affinity. This antagonism may contribute to its efficacy in treating schizophrenia. 2 2
From the Research
Relationship between Olanzapine and Dopamine
- Olanzapine is an atypical antipsychotic with a multireceptorial binding profile, including a greater affinity for serotonin 5-HT2A than for dopamine D2 receptors 3, 4.
- The exact mechanism of olanzapine's action on dopamine is not fully understood, but it is believed to contribute to its antipsychotic effects 3.
- Olanzapine's affinity for dopamine D2 receptors is lower than its affinity for serotonin 5-HT2A receptors, which may help to explain its lower risk of extrapyramidal side effects compared to typical antipsychotics 3, 5.
- The relationship between olanzapine and dopamine is complex and may involve multiple neurotransmitter systems, including serotonin and dopamine 3, 4.
Clinical Implications
- Olanzapine's unique binding profile and mechanism of action may contribute to its efficacy in treating schizophrenia and bipolar disorder 3, 6, 4.
- The drug's lower risk of extrapyramidal side effects compared to typical antipsychotics makes it a useful option for patients who are sensitive to these effects 3, 5.
- However, olanzapine is associated with other side effects, such as weight gain and metabolic syndrome, which must be carefully monitored and managed 7, 6, 4.