Femoxetine

Femoxetine (INN; tentative brand name Malexil; developmental code name FG-4963) is a drug related to paroxetine that was being developed as an antidepressant by Danish pharmaceutical company Ferrosan in 1975 before acquisition of the company by Novo Nordisk. It acts as a selective serotonin reuptake inhibitor (SSRI). Development was halted to focus attention on paroxetine instead, as femoxetine could not be administered as a daily pill.

Femoxetine

Clinical data
Routes of administration	Oral
ATC code	None
Legal status
Legal status	In general: uncontrolled
Pharmacokinetic data
Elimination half-life	7–27 hours
Identifiers
IUPAC name (3R,4S)-3-[(4-methoxyphenoxy)methyl]-1-methyl-4-phenyl-piperidine
CAS Number	59859-58-4 Y
PubChem CID	3012003
ChemSpider	2280941 Y
UNII	8Y719ZLX8C
ChEMBL	ChEMBL94739 Y
CompTox Dashboard (EPA)	DTXSID70208576
Chemical and physical data
Formula	C20H25NO2
Molar mass	311.425 g·mol−1
3D model (JSmol)	Interactive image
SMILES O(c1ccc(OC)cc1)C[C@@H]3[C@@H](c2ccccc2)CCN(C)C3
InChI InChI=1S/C20H25NO2/c1-21-13-12-20(16-6-4-3-5-7-16)17(14-21)15-23-19-10-8-18(22-2)9-11-19/h3-11,17,20H,12-15H2,1-2H3/t17-,20-/m1/s1 Y Key:OJSFTALXCYKKFQ-YLJYHZDGSA-N Y
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Both femoxetine and paroxetine were invented in the 1970s. Jørgen Anders Christensen's name is on the patents^[1][2] and Jorgen Buus-Lassen's name is on the pharmacology paper.^[3]

After Ferrosan's acquisition, femoxetine died from neglect.^[4]

In a separate patent, Ferrosan stated that Femoxetine could be used as an appetite suppressant,^[5] using ten times the dosage than for paroxetine, 300 - 400mg daily.

Femoxetine has the same stereochemical properties as Nocaine, another agent with a similar structure claimed to have been synthesized using arecoline as the starting alkaloid.^{[citation needed]}

Analogs

1. Addition of the para-fluoro atom results in a different compound that is a hybrid of femoxetine & paroxetine named FG 7080,^[6] which has a separate patent.^[7] According to the patent tables, incorporation of the fluorine atom potentiated the 5-HT affinity considerably.
2. Pfizer made some similar analogs^[8] E.g. a Viloxazine type of catechol ether is used, but 4-phenyl instead of based on a morpholine ring.
3. NNC-63-0780.^[9][10] binds to ORL1 instead of SERT.

• NNC 09-0026

See also

• Alaproclate
• Indalpine
• Zimelidine

References

1. U.S. patent 3,912,743
2. U.S. patent 4,007,196
3. Lassen JB, Petersen E, Kjellberg B, Olsson SO (May 1975). "Comparative studies of a new 5HT-uptake inhibitor and some tricyclic thymoleptics". European Journal of Pharmacology. 32 (1): 108–15. doi:10.1016/0014-2999(75)90329-5. PMID 1149822.
4. Healy D (2004). Let them eat Prozac: the unhealthy relationship between the pharmaceutical industry and depression. New York, NY: New York Univ. Press. pp. 26–27. ISBN 9780814736692. Jørgen Buus Lassen femoxetine.
5. U.S. patent 4,442,113
6. "(3S,4R)-4-(4-Fluorophenyl)-3-[(4-methoxyphenoxy)methyl]piperidine". PubChem. U.S. National Library of Medicine.
7. U.S. patent 4,585,777
8. U.S. patent 20,070,142,389
9. Bignan GC, Connolly PJ, Middleton SA (2005). "Recent advances towards the discovery of ORL-1 receptor agonists and antagonists". Expert Opinion on Therapeutic Patents. 15 (4): 357–388 6. doi:10.1517/13543776.15.4.357. S2CID 94720416.
10. "CID:9862655". PubChem. U.S. National Library of Medicine.