mCPP is thought to be formed from nefazodone specifically by CYP2D6.The ratios of brain-to-plasma concentrations of mCPP to nefazodone are 47:1 in mice and 10:1 in rats, suggesting that brain exposure to mCPP may be much higher than plasma exposure. Conversely, hydroxynefazodone levels in the brain are 10% of those in plasma in rats. As such, in spite of its relatively low plasma concentrations, brain exposure to mCPP may be substantial, whereas that of hydroxynefazodone may be minimal. Chemistry
Nefazodone is a phenylpiperazine; it is an alpha-phenoxyl derivative of etoperidone which in turn was a derivative of trazodone. History
Nefazodone was discovered by scientists at Bristol-Myers Squibb (BMS) who were seeking to improve on trazodone by reducing its sedating qualities.BMS obtained marketing approvals worldwide for nefazodone in 1994. It was marketed in the US under the brand name Serzone and in Europe under the brand name Dutonin.In 2002 the FDA obligated BMS to add a black box warning about potential fatal liver toxicity to the drug label. Worldwide sales in 2002 were $409 million.In 2003 Public Citizen filed a citizen petition asking the FDA to withdraw the marketing authorization in the US, and in early 2004 the organization sued the FDA to attempt to force withdrawal of the drug. The FDA issued a response to the petition in June 2004 and filed a motion to dismiss, and Public Citizen withdrew the suit.Generic versions were introduced in the US in 2003 and Health Canada withdrew the marketing authorization that year.Sales of nefazodone were about $100 million in 2003.
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.