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What is Nefazodone and explain in detail?
Nefazodone, sold formerly under the brand names Serzone, Dutonin, and Nefadar among others, is an atypical antidepressant which was first marketed by Bristol-Myers Squibb (BMS) in 1994 but has since largely been discontinued. BMS withdrew it from the market by 2004 due to decreasing sales due to the rare incidence of severe liver damage and the onset of generic competition. The incidence of severe liver damage is approximately 1 in every 250,000 to 300,000 patient-years. Generic versions were introduced in 2003.Nefazodone is a phenylpiperazine compound and is related to trazodone. It has been described as a serotonin antagonist and reuptake inhibitor (SARI) due to its combined actions as a potent serotonin 5-HT2A receptor and 5-HT2C receptor antagonist and weak serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI).

Medical uses
Nefazodone is used to treat major depressive disorder, aggressive behavior, anxiety, and panic disorder.

Available forms
Nefazodone is available as 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg tablets for oral ingestion.

Contraindications
Side effects
Nefazodone can cause severe liver damage, leading to a need for liver transplant, and death. The incidence of severe liver damage is approximately 1 in every 250,000 to 300,000 patient-years. By the time that it started to be withdrawn in 2003, nefazodone had been associated with at least 53 cases of liver injury, with 11 deaths, in the United States, and 51 cases of liver toxicity, with 2 cases of liver transplantation, in Canada. In a Canadian study which found 32 cases in 2002, it was noted that databases like that used in the study tended to include only a small proportion of suspected drug reactions.Protocols are that nefazodone should not be used in patients who have a pre-existing liver condition. Prior to treatment liver enzymes should be tested to make sure there is not an underlying liver condition.  If serum AST or serum ALT levels are more than 3 times the upper limit of normal (ULN) should be permanently withdrawn from the drug.  Regular enzyme labs should be done every 6 months.  Due to liver issues Nefazodone should not be a first line treatment. Common and mild side effects of nefazodone reported in clinical trials more often than placebo include dry mouth (25%), sleepiness (25%), nausea (22%), dizziness (17%), blurred vision (16%), weakness (11%), lightheadedness (10%), confusion (7%), and orthostatic hypotension (5%). Rare and serious adverse reactions may include allergic reactions, fainting, painful/prolonged erection, and jaundice.Nefazodone is not especially associated with increased appetite and weight gain.

Interactions
Nefazodone is a potent inhibitor of CYP3A4, and may interact adversely with many commonly used medications that are metabolized by CYP3A4.

Pharmacology
Pharmacodynamics
Nefazodone acts primarily as a potent antagonist of the serotonin 5-HT2A receptor and to a lesser extent of the serotonin 5-HT2C receptor. It also has high affinity for the α1-adrenergic receptor and serotonin 5-HT1A receptor, and relatively lower affinity for the α2-adrenergic receptor and dopamine D2 receptor. Nefazodone has low but significant affinity for the serotonin, norepinephrine, and dopamine transporters as well, and therefore acts as a weak serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It has low but potentially significant affinity for the histamine H1 receptor, where it is an antagonist, and hence may have some antihistamine activity. Nefazodone has negligible activity at muscarinic acetylcholine receptors, and accordingly, has no anticholinergic effects.

Pharmacokinetics
The bioavailability of nefazodone is low and variable, about 20%. Its plasma protein binding is approximately 99%, but it is bound loosely.Nefazodone is metabolized in the liver, with the main enzyme involved thought to be CYP3A4. The drug has at least four active metabolites, which include hydroxynefazodone, para-hydroxynefazodone, triazoledione, and meta-chlorophenylpiperazine. Nefazodone has a short elimination half-life of about 2 to 4 hours. Its metabolite hydroxynefazodone similarly has an elimination half-life of about 1.5 to 4 hours, whereas the elimination half-lives of triazoledione and mCPP are longer at around 18 hours and 4 to 8 hours, respectively. Due to its long elimination half-life, triazole is the major metabolite and predominates in the circulation during nefazodone treatment, with plasma levels that are 4 to 10 times higher than those of nefazodone itself. Conversely, hydroxynefazodone levels are about 40% of those of nefazodone at steady state