Doxepin hydrochloride

Names

[ Name ]:
Doxepin hydrochloride

[Synonym ]:
P 3693A
Curatin
3-(Dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine hydrochloride (1:1)
1-Propanamine, 3-dibenz[b,e]oxepin-11(6H)-ylidene-N,N-dimethyl-, hydrochloride (1:1)
3-(Dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethyl-1-propanamine hydrochloride (1:1)
Doxepin hydrochloride
EINECS 214-966-8
Adapin
N,N-Dimethyldibenz[b,e]oxepin-D11(6H),g-propylamine Hydrochloride
3-Dibenzo[b,e]oxepin-11(6H)-yliden-N,N-dimethylpropan-1-aminhydrochlorid
Quitaxon
MFCD00079135
1-propanamine, 3-dibenz[b,e]oxepin-11(6H)-ylidene-N,N-dimethyl-, hydrochloride
doxepin HCl
Novoxapin [Ester]
11-(3-Dimethylaminopropylidene)-6,11-dihydrodibenzo[b,e]oxepine Hydrochloride
MF 10 HCl
3-dibenzo[b,e]oxepin-11(6H)-ylidene-N,N-dimethylpropan-1-amine hydrochloride
N,N-Dimethyldibenz[b,e]oxepin-δ11(6H),γ-propylamine hydrochloride
Novoxapin
11-(3-Dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepine hydrochloride
3-(dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine hydrochloride
Doxepin (Hydrochloride)

Biological Activity

[Description]:

Doxepin HCl is a tricyclic antidepressant that is marketed worldwide.Target: SSRIsDoxepin inhibits the reuptake of serotonin and norepinephrine and acts as a antagonist at various serotonergic, adrenergic, musacrinic, dopaminergic and histaminergic receptors [1]. In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p < or = .001) and subchronic (night 28, p < or = .05) intake compared with the patients who received placebo (N = 20, 47.4+/-16.8 years of age). Doxepin to cause significantly (p < or = .05) better global improvement at the first day of treatment [2].

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> Serotonin Transporter

Research Areas >> Neurological Disease

[References]

[1]. http://pdsp.med.unc.edu/pdsp.php

[2]. Hajak, G., et al., Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study. J Clin Psychiatry, 2001. 62(6): p. 453-63.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
413.3ºC at 760mmHg

[ Melting Point ]:
187-189°C

[ Molecular Formula ]:
C₁₉H₂₂ClNO

[ Molecular Weight ]:
315.837

[ Flash Point ]:
121.3ºC

[ Exact Mass ]:
315.138977

[ PSA ]:
12.47000

[ LogP ]:
4.76440

[ Vapour Pressure ]:
4.87E-07mmHg at 25°C

[ Stability ]:
Store in Freezer at -20°C

[ Water Solubility ]:
1 M HCl: 50 mg/mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HQ4375000

CHEMICAL NAME :: Dibenz(b,e)oxepin-delta(sup 11(6H),gamma)-propylamine, N,N-dimethyl-, hydrochloride

CAS REGISTRY NUMBER :: 1229-29-4

LAST UPDATED :: 199706

DATA ITEMS CITED :: 29

MOLECULAR FORMULA :: C19-H21-N-O.Cl-H

MOLECULAR WEIGHT :: 315.87

WISWESSER LINE NOTATION :: T C676 IO&T&J B3N1&1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 357 ug/kg

TOXIC EFFECTS :: Behavioral - muscle weakness Behavioral - coma Vascular - BP lowering not characterized in autonomic section

REFERENCE :: JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 7,161,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 112 mg/kg/4W-I

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions

REFERENCE :: JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 44,106,1983

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 90 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - coma Blood - hemorrhage

REFERENCE :: JATOD3 Journal of Analytical Toxicology. (Preston Pub. Inc., POB 48312, Niles, IL 60648) V.1- 1977- Volume(issue)/page/year: 2,18,1978

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 9300 ug/kg

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Behavioral - muscle contraction or spasticity Cardiac - change in rate

REFERENCE :: JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883- Volume(issue)/page/year: 237,2632,1977

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 141 mg/kg/12W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Ear) - tinnitus

REFERENCE :: SMJOAV Southern Medical Journal. (Southern Medical Assoc., POB 2446, Birmingham, AL 35205) V.1- 1908- Volume(issue)/page/year: 76,1204,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 357 ug/kg

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), zonal Liver - jaundice (or hyperbilirubinemia) hepatocellular

REFERENCE :: ANZJB8 Australian and New Zealand Journal of Medicine. (Modern Medicine of Australia Pty., Ltd., 100 Pacific Highway, North Sydney, 2060, Australia) V.1- 1971- Volume(issue)/page/year: 23,523,1993

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 147 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,72,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 84 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 155 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 13 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,72,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 180 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 79 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,72,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 160 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,72,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 15 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,72,1972

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 300 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >27 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 20400 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Vascular - BP lowering not characterized in autonomic section

REFERENCE :: IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 22,539,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 11 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,72,1972 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 14560 mg/kg/26W-C

TOXIC EFFECTS :: Cardiac - changes in heart weight Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,929,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3300 mg/kg/33D-C

TOXIC EFFECTS :: Gastrointestinal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 6,889,1972 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1620 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1620 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 60 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 540 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,913,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 210 mg/kg

SEX/DURATION :: female 8-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth)

REFERENCE :: DPTHDL Developmental Pharmacology and Therapeutics. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.1- 1980- Volume(issue)/page/year: 8,17,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 900 mg/kg

SEX/DURATION :: female 8-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,905,1971

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 45 mg/kg

SEX/DURATION :: female 8-16 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 5,905,1971 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3181 No. of Facilities: 140 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 2633 (estimated) No. of Female Employees: 1442 (estimated)

Safety Information

[ Symbol ]:

GHS02, GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H225-H301 + H311 + H331-H370

[ Precautionary Statements ]:
P210-P260-P280-P301 + P310-P311

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ Hazard Codes ]:
T,F

[ Risk Phrases ]:
R25

[ Safety Phrases ]:
36/37/39-45

[ RIDADR ]:
UN 2811 6.1/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
HQ4375000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
2932999099

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2932999099

[ Summary ]:
2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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