Description
Nefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries, due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in 250,000 to 300,000 patient-years. On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States. [Wikipedia]
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Hepatic. Route of Elimination: Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged in urine. Half Life: 2-4 hours
- Uses/Sources: Nefazodone (sold as Serzone, Nefadar) is a psychoactive drug and antidepressant. [wikipedia]
- Health Effects: Serious side effects include an allergic reaction, fainting, or painful/prolonged erection. [Wikipedia]
- Symptoms: Cases of life-threatening hepatic failure have been reported in patients treated with nefazodone.
- Treatment: Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. Due to the wide distribution of nefazodone in body tissues, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for nefazodone are known. (L1712)
- Route of Exposure: Nefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%).
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Potassium voltage-gated channel subfamily H member 2 Cytochrome P450 3A4 Muscarinic acetylcholine receptor M2 Multidrug resistance protein 1 5-hydroxytryptamine receptor 2C 5-hydroxytryptamine receptor 1A Alpha-2A adrenergic receptor Sodium-dependent dopamine transporter Histamine H1 receptor |
9537821 9400006 24374264 22409598 9871604 18083778 11452702 7855217 11752352 16433010 |
|
5-hydroxytryptamine receptor 2A Sodium-dependent serotonin transporter Alpha-1A adrenergic receptor Sodium-dependent noradrenaline transporter Alpha-1B adrenergic receptor |
Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT2) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant. |
17016423 21823597 9537821 9400006 12873632 9871604 17139284 7475971 9472845 10577608 11752352 10435395 14520130 10512149 10220119 |