nefazodone
Trade name: serzone
Approved
Dec 22, 1994
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. 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. — NCATS
Clinical trial activity
5 trials · 6 clinical orgs · 12 marketing orgs
Earliest trial started Dec 1, 1996 (NCT00000286)
Timeline
1990s
- Dec 22, 1994
Bristol-Myers Squibb — Earliest FDA Approval
- Dec 22, 1994
Bristol-Myers Squibb — NDA Organization
- Jan 1, 1996
Earliest Phase 2 Sponsor(trial)
- Jan 1, 1999
Earliest Phase 3 Sponsor(trial)
2000s
- Jan 14, 2003
Roxane Laboratories — Marketing Organization
- Jan 14, 2003
Boehringer Ingelheim — Marketing Organization
- Sep 16, 2003
Aurobindo Pharma — Marketing Organization
- Sep 16, 2003
Ani Pharmaceuticals — Marketing Organization
- Sep 16, 2003
Dr. Reddy's Laboratories — Marketing Organization
- Sep 16, 2003
Fosun — Marketing Organization
- Sep 16, 2003
Mylan — Marketing Organization
- Sep 16, 2003
Sun Pharmaceuticals — Marketing Organization
- Sep 16, 2003
Teva — Marketing Organization
- Sep 16, 2003
Watson Pharmaceuticals — Marketing Organization
- Sep 16, 2003
Chartwell Pharmaceuticals — Marketing Organization
Indications
Mechanism of action
- Serotonin 2c (5-HT2c) receptorANTAGONIST
HTR2C antagonist
- Serotonin 2a (5-HT2a) receptorANTAGONIST
HTR2A antagonist
- Norepinephrine transporterINHIBITOR
SLC6A2 inhibitor
- Serotonin transporterINHIBITOR
SLC6A4 inhibitor
Approval history
- approvedDec 22, 1994
Chemistry & pharmacology
SMILES
CCc1nn(CCCN2CCN(c3cccc(Cl)c3)CC2)c(=O)n1CCOc1ccccc1- Mol. weight
- 470.02 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- No
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
- Delivery
- Oral
- Availability
- Prescription Only
Oral
Yes
Parenteral
No
Topical
No
Sources
- ChEMBLCHEMBL623 ↗
- WikipediaNefazodone ↗
- NCATS27X63J94GR ↗
- ChEMBLCHEMBL2110615 ↗
- ChEMBLCHEMBL2105036 ↗
- ChEMBLCHEMBL1200492 ↗
Also known as
- 1-(3-(4-(m-chlorophenyl)-1-piperazinyl)propyl)-3-ethyl-4-(2-phenoxyethyl)-delta2-1,2,4-triazolin-5-one
- 1-(3-(4-(m-chlorophenyl)-1-piperazinyl)propyl)-3-ethyl-4-(2-phenoxyethyl)-delta2-1,2,4-triazolin-5-one
- apo-nefazodone
- apotex brand of nefazodone hydrochloride
- bmy-13754
- bmy-13754
- bristol-myers brand of nefazodone hydrochloride
- bristol-myers squibb brand of nefazodone hydrochloride
- dutonin
- dutonin
- dutonin
- europharma brand of nefazodone hydrochloride
- hormosan brand of nefazodone hydrochloride
- lin-nefazodone
- linson pharma brand of nefazodone hydrochloride
- menarini brand of nefazodone hydrochloride
- menfazona
- mj-13754-1
- mj-13754-1
- nefadar
- nefazodona
- nefazodona
- nefazodone
- nefazodone
- nefazodone
- nefazodone
- nefazodone
- nefazodone
- nefazodone
- nefazodone
- nefazodone
- nefazodone
- nefazodone hcl
- nefazodone hcl
- nefazodone hcl
- nefazodone hydrochloride
- nefazodone hydrochloride
- nefazodone hydrochloride
- nefazodone hydrochloride
- nefazodone hydrochloride
- nefazodonum
- nefazodonum
- rulivan
- serzone
- serzone
- serzone
- serzone
- serzone
- serzone
- serzone
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT00231348 | Phase 4 | Oct 3, 2005 | Bristol-Myers Squibb, Emory University |
| NCT00249509 | Phase 2 | Sep 1, 2000 | Columbia University, National Institute on Drug Abuse (NIDA) |
| NCT00000293 | Phase 3 | Jan 1, 1999 | National Institute on Drug Abuse (NIDA), University of Minnesota |
| NCT00015210 | Phase 2 | Feb 1, 1997 | Boston University |
| NCT00000286 | Phase 2 | Dec 1, 1996 | National Institute on Drug Abuse (NIDA), University of Minnesota |
Organizations
Research & Development (6)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| National Institute on Drug Abuse (NIDA) | Government | 3 | 3 | 2 | 1996 |
| University of Minnesota | Academic/Hospital | 2 | 0 | 2 | 1996 |
| Boston University | Academic/Hospital | 1 | 1 | 1 | 1997 |
| Bristol-Myers Squibb | For profit | 1 | 0 | 1 | 2005 |
| Columbia University | Academic/Hospital | 1 | 0 | 1 | 2000 |
| Emory University | Academic/Hospital | 1 | 1 | 1 | 2005 |
Marketing (15)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Ani Pharmaceuticals | For profit | MKTG | Sep 16, 2003 |
| Ani Pharmaceuticals | For profit | SYN | Sep 16, 2003 |
| Aurobindo Pharma | For profit | MKTG | Sep 16, 2003 |
| Boehringer Ingelheim | For profit | MKTG | Jan 14, 2003 |
| Bristol-Myers Squibb | For profit | SYN | Dec 22, 1994 |
| Bristol-Myers Squibb | For profit | NDA | Dec 22, 1994 |
| Chartwell Pharmaceuticals | For profit | MKTG | Sep 16, 2003 |
| Dr. Reddy's Laboratories | For profit | MKTG | Sep 16, 2003 |
| Fosun | For profit | MKTG | Sep 16, 2003 |
| Mylan | For profit | MKTG | Sep 16, 2003 |
| Roxane Laboratories | For profit | MKTG | Jan 14, 2003 |
| Sun Pharmaceuticals | For profit | MKTG | Sep 16, 2003 |
| Teva | For profit | SYN | Jun 11, 2003 |
| Teva | For profit | MKTG | Sep 16, 2003 |
| Watson Pharmaceuticals | For profit | MKTG | Sep 16, 2003 |