Doxepin

Doxepin inhibits reuptake of serotonin and norepinephrine as a tricyclic antidepressant. Doxepin has therapeutic effects in atopic dermatitis，chronic urticarial，can improve cognitive processes， protect central nervous system. Doxepin has also been proposed as a protective factor against oxidative stress[1][2][3].

Signaling Pathways >> PI3K/Akt/mTOR >> mTOR

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Research Areas >> Neurological Disease

The protective effect of doxepin is associated with the enhancement of PSD-95 and synapsin 1 expression via PI3K/AKT/mTOR signaling pathway[4]. Western Blot Analysis[4] Cell Line: SH-SY5Y human neuroblastoma cell line Concentration: 10 ng/mL Incubation Time: 2 h Result: Improved the protein expre-ssion levels of PSD-95, synapsin 1 and p-AKT in SH-SY5Y cells, and decreased the protein expression level of p-mTOR in SH-SY5Y cells.

Doxepin (intraperitoneal injection of 1 mg/kg and 5 mg/kg doxepin once a day for 21 days) can protect against the Aβ1-42-induced memory impairment in rats[4]. Animal Model: SD male rats[4] Dosage: 1, 5mg/kg Administration: Doxepin (intraperitoneal injection of 1 mg/kg and 5 mg/kg doxepin once a day for 21 days) Result: Improved the protein expression levels of PSD-95 and synapsin 1 in hippocampus and tem-poral lobe, and decreased the protein expression level of p-AKT in hippocampus and temporal lobe after treatment of 1 mg/kg of doxepin.

[1]. AnnemiekVermeeren, et al. Effects of the use of hypnotics on cognition. Progress in brain research vol. 190 (2011): 89-103.

[2]. G Hajak, et al. Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study. The Journal of clinical psychiatry vol. 62,6 (2001): 453-63.

[3]. Mahsa Gharzi, et al. Effects of different doses of doxepin on passive avoidance learning in rats. Advanced biomedical research vol. 2 66. 30 Jul. 2013.

[4]. Jimei Bu, et al. Mechanism underlying the effects of doxepin on β-amyloid -induced memory impairment in rats. Iran J Basic Med Sci. 2017 Sep;20(9):1044-1049.

MOLECULAR FORMULA :

C19-H21-N-O

MOLECULAR WEIGHT :

279.41

WISWESSER LINE NOTATION :

T C676 BY IO JHJ BU3N1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

60 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - bronchiectasis

REFERENCE :

CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 10,327,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

147 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - parasympatholytic Behavioral - somnolence (general depressed activity)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

182 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - parasympatholytic Behavioral - somnolence (general depressed activity)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

16 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - parasympatholytic Behavioral - somnolence (general depressed activity)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

135 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - parasympatholytic Behavioral - somnolence (general depressed activity)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

79 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - parasympatholytic Behavioral - somnolence (general depressed activity)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

26 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - parasympatholytic Behavioral - somnolence (general depressed activity)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

11 mg/kg

TOXIC EFFECTS :

Autonomic Nervous System - parasympatholytic Behavioral - somnolence (general depressed activity)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 15,863,1965