|AHFS/Drugs.com||Consumer Drug Information|
|ATC code||N05AE05 (WHO)|
|Biological half-life||18 hours|
|Excretion||Faecal (~80%), renal (~9%)|
|Chemical and physical data|
|Molar mass||492.68 g/mol|
|3D model (Jmol)||Interactive image|
|Specific rotation||[α]20D −59°|
|Melting point||176 to 178 °C (349 to 352 °F)|
|Solubility in water||45 mg/mL (20 °C)|
Lurasidone // (trade name Latuda) is an atypical antipsychotic developed by Dainippon Sumitomo Pharma and marketed by Sunovion in the USA. In the USA since 2013, it is also approved for the treatment of depressive episodes associated with bipolar I disorder as well as bipolar II disorder in adults when used alone or in combination with lithium, valproate, or lamotrigine.
Lurasidone is FDA approved for the treatment of schizophrenia since 2010 and depressive episodes associated with bipolar I disorder since 2013. It received regulatory approval in the UK in September 2014. In October 2014, NHS Scotland advised use of lurasidone for schizophrenic adults who have not seen improvements with previous antipsychotics due to problems that arise from weight gain or changes in metabolic pathways when taking other medications. It received EMA approval on January 24, 2014. It was launched in Canada for the treatment of schizophrenia in September 2012, Health Canada giving their Summary Basis of Decision (SBD) as favourable on October 15, 2012. European Commission has granted a marketing authorization for once-daily oral lurasidone for the treatment of schizophrenia in adults. It is approved for use in the EU.
In July 2013 lurasidone received approval for bipolar I depression. Few available atypical antipsychotics are known to possess antidepressant efficacy in bipolar disorder (with the notable exceptions being quetiapine, olanzapine and possibly asenapine) as a monotherapy, even though the majority of atypical antipsychotics are known to possess significant antimanic activity, which is yet to be clearly demonstrated for lurasidone.
Lurasidone may be useful for treating the cognitive and memory deficits seen in schizophrenia. In animal studies, it reversed dizocilpine-induced learning and memory impairment and was found to be superior in doing this to all of the other antipsychotics examined, including risperidone, olanzapine, quetiapine, clozapine, aripiprazole, and haloperidol. Lurasidone has activity at several serotonin receptors that are involved in learning and memory, and unlike most other antipsychotics, lacks any anticholinergic effects (which are known to impair cognitive processes and memory). These properties may underlie its improved effectiveness in treating these symptoms relative to older agents.
Lurasidone is not approved by the Food and Drug Administration (FDA) for the treatment of behavior disorders in older adults with dementia.
Lurasidone is contraindicated in individuals who are taking strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir, levodropropizine, etc.) or inducers (carbamazepine, St. John's wort, phenytoin, rifampicin etc.). The use of lurasidone in pregnant women has not been studied and is not recommended, although it should be noted that it is a category B drug. Excretion in breast milk is also unknown; lurasidone is not recommended for breastfeeding women. In the United States it is not indicated for use in children.
Side effects are generally similar to other antipsychotics. The drug has a relatively well-tolerated side effect profile, with low propensity for QTc interval changes, weight gain and lipid-related adverse effects. In a recent meta-analysis of the efficacy and tolerability of 15 antipsychotic drugs it was found to produce the second least (after haloperidol) weight gain, the least QT interval prolongation, the fourth most extrapyramidal side effects (after haloperidol, zotepine and chlorpromazine) and the sixth least sedation (after paliperidone, sertindole, amisulpride, iloperidone and aripiprazole).
As with other atypical neuroleptics, lurasidone should be used with caution in the elderly because it puts them at an increased risk for a stroke or transient ischemic attack; however, these risks are not likely to be greater than those associated with antipsychotics of other classes. Similarly, lurasidone should not be used to treat dementia-related psychosis, as evidence has shown increased mortality with antipsychotic use.
Latuda is mainly blocking the D2 receptor (high affinity for D2 receptors). Also the dopamine D3 and D4-receptors have some importance. Blocks of 5HT2A and 5HT7 receptor. High affinity for 5HT2A receptor and 5HT7, for those two. Partial agonism for the 5HT1A receptor. Low affinity for the 5HT2C receptor, 5HT3 and 5HT4-receptor. No affinity to H1-receptors. Low affinity at noradrenaline.
Latuda has high affinity for D2 receptors, 5HT2A and 5HT7 receptor. No affinity for the H1 receptor and low affinity for 5HT2C explains the low weight gain, with latuda. However, there is an affinity for the 5HT3 receptor (but low affinity). That Latuda touch the 5HT3-receptor removes risk for prolonged QTc-intervalls. Norepinephrine is touched a bit.
Mechanism of action
Lurasidone acts as an antagonist of the following sites:
- α1-adrenergic receptor (Ki = 48 nM)
- α2A-adrenergic receptor (Ki = 1.6 nM)
- α2C-adrenergic receptor (Ki = 10.8 nM)
- D1 receptor (Ki = 262 nM)
- D2 receptor (Ki = 1.7 nM)
- D3 receptor
- D4 receptor
- 5-HT2A receptor (Ki = 2.0 nM)
- 5-HT2C receptor (Ki = 415 nM)
- 5-HT3 receptor
- 5-HT4 receptor
- 5-HT7 receptor (Ki = 0.5 nM)
And as a partial agonist of the following sites:
- 5-HT1A receptor (Ki = 6.8 nM)
Lurasidone is metabolized in the liver via the enzyme CYP3A4. This means that its plasma concentrations may be increased when combined with CYP3A4 inhibitors like ketoconazole or grapefruit juice, possibly leading to more side effects. Co-administration of CYP3A4 inducers like rifampicin or St. John's wort can reduce plasma levels and consequently decrease the effects of the drug.
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- Pregnancy category
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