Cidoxepin

Cidoxepin (former developmental code name P-4599), also known as cis-doxepin or (Z)-doxepin, is a tricyclic antidepressant which was developed in the 1960s but was never marketed.^[1][2] It is the cis or (Z) stereoisomer of doxepin, a mixture of (E) and (Z) isomers that is used commercially in a ratio of approximately 85:15 with cidoxepin as a relatively minor constituent.^[1][3] However, the drug has similar activity to that of doxepin, acting as a serotonin–norepinephrine reuptake inhibitor, H₁ receptor antagonist, and anticholinergic, and notably is thought to have more antidepressant activity than trans-doxepin.^[3][4][5] The central anticholinergic activity of cidoxepin has been reported to be 3-fold greater than that of the trans isomer in mice.^[5]

Cidoxepin

Clinical data
Other names	(Z)-Doxepin; cis-Doxepin; P-4599
Identifiers
IUPAC name (3Z)-3-(6H-Benzo[c][1]benzoxepin-11-ylidene)-N,N-dimethylpropan-1-amine
CAS Number	3607-18-9
PubChem CID	667468
ChemSpider	580850
UNII	F96TTB8728
ChEBI	CHEBI:36691
CompTox Dashboard (EPA)	DTXSID301318253
Chemical and physical data
Formula	C19H21NO
Molar mass	279.383 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN(C)CC/C=C\1/C2=CC=CC=C2COC3=CC=CC=C31
InChI InChI=1S/C19H21NO/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11- Key:ODQWQRRAPPTVAG-BOPFTXTBSA-N

Cidoxepin has recently been reinvestigated and is now currently under development as an antihistamine by Elorac, Inc. for the treatment of chronic urticaria (hives).^[4] As of 2017, it is in phase II clinical trials for this indication.^[4] The drug was also under investigation for the treatment of allergic rhinitis (hay fever), atopic dermatitis (atopic eczema), and contact dermatitis, but development for these indications was discontinued.^[4]