Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Hepatic Route of Elimination: Approximately 50% of the administered dose is excreted in the urine and 30% in the feces. Half Life: 8 hours (range 4-12 hours)
- Uses/Sources: For use in patients with treatment-resistant schizophrenia.
- Health Effects: Clozapine may cause side effects; most are minor, although some are serious and potentially fatal. Common side effects include extreme constipation, bed-wetting, night-time drooling, muscle stiffness, sedation, tremors, orthostatic hypotension, hyperglycemia, and weight gain. The risk of developing extrapyramidal symptoms such as tardive dyskinesia is below that of typical antipsychotics; this may be due to clozapine's anticholinergic effects. Extrapyramidal symptoms may subside somewhat after a person switches from another antipsychotic to clozapine. Clozapine also carries five black box warnings, including warnings for agranulocytosis, CNS depression, leukopenia, neutropenia, seizure disorder, bone marrow suppression, dementia, hypotension, myocarditis, orthostatic hypotension (with or without syncope) and seizures. Lowering of the seizure threshold may be dose related and slow initial titration of dose may decrease the risk for precipitating seizures. Slow titration of dosing may also decrease the risk for orthostatic hypotension and other adverse cardiovascular side effects. Many male patients have experienced cessation of ejaculation during orgasm as a side effect of clozapine, though this is not documented in official drug guides. (Wikipedia)
- Treatment: Establish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. (L1712)
- Route of Exposure: Oral; rapid and almost complete.
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Potassium voltage-gated channel subfamily H member 2 Muscarinic acetylcholine receptor M2 Muscarinic acetylcholine receptor M3 Muscarinic acetylcholine receptor M4 Muscarinic acetylcholine receptor M5 5-hydroxytryptamine receptor 1B 5-hydroxytryptamine receptor 1D Alpha-1B adrenergic receptor Alpha-2B adrenergic receptor Alpha-2C adrenergic receptor 5-hydroxytryptamine receptor 1E Adenosine receptor A3 |
19110341 15745831 12190308 18448342 15911273 16250647 12873512 17848919 |
|
Muscarinic acetylcholine receptor M1 Alpha-1A adrenergic receptor Alpha-2A adrenergic receptor 5-hydroxytryptamine receptor 7 D(3) dopamine receptor 5-hydroxytryptamine receptor 3A D(1B) dopamine receptor 5-hydroxytryptamine receptor 6 |
The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism. |
9406603 16983399 11997696 10377229 19696922 14578406 |
5-hydroxytryptamine receptor 2A 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A D(2) dopamine receptor D(4) dopamine receptor D(1A) dopamine receptor Histamine H1 receptor Neuron-specific vesicular protein calcyon Histamine H4 receptor |
The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism. |
13129658 16040180 22243698 15286066 14530903 15886414 12589516 12763097 15037867 12769622 14751426 11752352 1352677 16854056 11997696 15992586 17346280 14575800 12973385 16860312 16223700 8831770 10377229 14687870 15781964 15213359 9822559 16983399 17382376 9622542 15261283 16220969 12923612 12564641 16182256 11052797 15917433 17145705 |