Drug Information

Drug (ID: DG01066) and It's Reported Resistant Information

• Name: Doxepin
• Synonyms: Doxepin; (e)-doxepin; trans-doxepin; 1668-19-5; Doxepinum [INN-Latin]; Doxepina [INN-Spanish]; UNII-851NLB57HQ; Sinequan; Sinequan (TN); 851NLB57HQ; Doxepin [USAN]; Doxepina; Doxepinum; (3e)-3-(Dibenzo[b,E]oxepin-11(6h)-Ylidene)-N,N-Dimethylpropan-1-Amine; 3607-34-9; 11-(3-Dimethylaminopropylidene)-6,11-dihydrodibenz(b,e)oxipin; Deptran; 1-Propanamine, 3-dibenz(b,e)oxepin-11(6H)-ylidene-N,N-dimethyl-; MF 10; Doxepin (INN); [11C]doxepin; 3-(Dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine; [11C]-doxepin; CCRIS 9176; Doxepin, (E)-; (3E)-3-(6H-benzo[c][1]benzoxepin-11-ylidene)-N,N-dimethylpropan-1-amine; HSDB 3069; Doxepin [INN:BAN]; NCGC00015344-03; CAS-1229-29-4; Methyllactate; 11-(3-(Dimethylamino)propylidene)-6H-dibenz(b,e)oxepine; 11-(3-Dimethylamino-propyliden)-6,11-dihydro-dibenz(b,e)oxipin; N,N-Dimethyldibenz(b,e)oxepin-delta(11(6H),gamma)-propylamine; E-DOXEPIN; Tocris-0508; P-3693A; Prestwick2_000263; Prestwick3_000263; Lopac-D-4526; CHEMBL860; Doxepin [USAN:INN:BAN]; Lopac0_000339; BSPBio_000106; SCHEMBL116895; BPBio1_000118; GTPL1225; GTPL3958; ZINC1331; (E)-3-(Dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine; DTXSID7022966; BDBM112780; Dibenz(b,e)oxepin-delta(sup 11(6H)),gamma-propylamine, N,N-dimethyl-; CCG-204434; SDCCGSBI-0050327.P002; NCGC00015344-01; NCGC00015344-02; NCGC00015344-04; NCGC00015344-12; NCGC00024623-01; NCGC00162127-01; US8629135, SW-07; C06971; D07875; L000699; BRD-K36616567-003-01-5; BRD-K54462405-003-03-3; BRD-K54462405-003-16-5; Q27077103; UNII-5ASJ6HUZ7D component ODQWQRRAPPTVAG-GZTJUZNOSA-N; 5EH
• Indication:
  In total 1 Indication(s)
  Depression [ICD-11: 6A70]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (3 diseases)
  Kidney injury [ICD-11: NB92]; [1]
  Nonalcoholic fatty liver disease [ICD-11: DB92]; [1]
  Type 2 diabetes mellitus [ICD-11: 5A11]; [1]
• Target: Histamine H1 receptor (H1R); HRH1_HUMAN; [1]
• Formula: C19H21NO
• IsoSMILES: CN(C)CC/C=C/1\\C2=CC=CC=C2COC3=CC=CC=C31
• 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+
• InChIKey: ODQWQRRAPPTVAG-GZTJUZNOSA-N
• PubChem CID: 667477
• TTD Drug ID: D06FES
• VARIDT ID: DR00542
• DrugBank ID: DB01142

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-05: Endocrine/nutritional/metabolic diseases

Type 2 diabetes mellitus [ICD-11: 5A11]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Facilitated glucose transporter member 4 (GLUT4) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Type 2 diabetes mellitus [ICD-11: 5A11.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Intraperitoneal glucose tolerance test (IPGTT)
• Mechanism Description: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice. Doxepin exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. Doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

ICD-13: Digestive system diseases

Nonalcoholic fatty liver disease [ICD-11: DB92]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Facilitated glucose transporter member 4 (GLUT4) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Nonalcoholic fatty liver disease [ICD-11: DB92.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Intraperitoneal glucose tolerance test (IPGTT)
• Mechanism Description: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice. Doxepin exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. Doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

ICD-22: Injury/poisoning/certain external causes consequences

Kidney injury [ICD-11: NB92]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Facilitated glucose transporter member 4 (GLUT4) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Kidney injury [ICD-11: NB92.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: AKT signaling pathway; Inhibition; hsa04151
• In Vivo Model: Male C57BL/6J mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Intraperitoneal glucose tolerance test (IPGTT)
• Mechanism Description: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice. Doxepin exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. Doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.

References

• Ref 1: Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice .Pharmaceuticals (Basel). 2021 Mar 16;14(3):267. doi: 10.3390/ph14030267. 10.3390/ph14030267