3435. Doxepin

Nomenclature

CAS number: 1668-19-5
3-Dibenz[b,e]oxepin-11(6H)-ylidene-N,N-dimethyl-1-propanamine; N,N-dimethyldibenz[b,e]oxepin-Δ11(6H),γ-propylamine; 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin; P-3693A.
C19H21NO; mol wt 279.38.
C 81.68%, H 7.58%, N 5.01%, O 5.73%.

Description and references

Seratonin and noradrenaline reuptake inhibitor with antihistaminic activity; tricyclic antidepressant. Prepn of mixture of cis- and trans-isomers: K. Stach, F. Bickelhaupt, Monatsh. Chem. 93, 896 (1962) DOI; F. Bickelhaupt et al., ibid. 95, 485 (1964) DOI; NL 6407758; K. Stach, US 3438981 (1965, 1969 both to Boehringer Mann.); and separation and activity of isomers: B. M. Bloom, J. R. Tretter, BE 641498; eidem, US 3420851 (1964, 1969 both to Pfizer). Pharmacology: A. Ribbentrop, W. Schaumann, Arzneim.-Forsch. 15, 863 (1965). Stereo-selective HPLC determn in plasma and urine: J. Yan et al., J. Chromatogr. B 691, 131 (1997) DOI. Review of pharmacology and therapeutic efficacy in depression: R. M. Pinder et al., Drugs 13, 161 (1977) DOI PubMed. Review of clinical efficacy in histamine mediated diseases and insomnia: H. Singh, P. M. Becker, Expert Opin. Invest. Drugs 16, 1295-1305 (2007) DOI PubMed.

Chemical structure

Properties

Oily liquid consisting of a mixture of cis- and trans-isomers. bp0.03 154-157°, bp0.2 260-270°. LD50 in mice, rats (mg/kg): 26, 16 i.v.; 79, 182 i.p.; 135, 147 orally (Ribbentrop, Schaumann).

Derivative

Hydrochloride.

Nomenclature

CAS number: 1229-29-4
Adapin (Fisons); Aponal (Novartis); Quitaxon (Napalm Sarl); Silenor (Somaxon); Sinequan (Pfizer).
C19H21NO.HCl; mol wt 315.84.
C 72.25%, H 7.02%, N 4.43%, O 5.07%, Cl 11.22%.

Properties

Crystals, mp 184-186°, 188-189°. Freely sol in alcohol.

Derivative

trans-Form hydrochloride.

Nomenclature

CAS number: 3607-18-9

Properties

mp 192-193°.

Derivative

cis-Form hydrochloride.

Nomenclature

CAS number: 25127-31-5
Cidoxepin hydrochloride; P-4599.

Properties

Crystals, mp 209-210.5°.

Therapeutic Category

Antidepressant.

Therapeutic Category (Veterinary)

Antipruritic.

Keywords

Antidepressant; Tricyclics ; Serotonin Noradrenaline Reuptake Inhibitor (SNRI)