Jump To Section:

Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (22)transporters (3) Show 25 proteins XML

enzymes (22)transporters (3) Show 25 proteins

Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2012-09-06 15:16:51 UTC

Update Date

2022-03-07 02:51:55 UTC

HMDB ID

HMDB0015273

Secondary Accession Numbers

HMDB15273

Metabolite Identification

Common Name

Doxepin

Description

Doxepin hydrochloride is a dibenzoxepin-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, doxepin does not affect mood or arousal, but may cause sedation. In depressed individuals, doxepin exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as doxepin and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H₁ receptors, α₁-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. Doxepin has less sedative and anticholinergic effects than amitriptyline. See toxicity section below for a complete listing of side effects. Doxepin may be used to treat depression and insomnia. Unlabeled indications include chronic and neuropathic pain, and anxiety. Doxepin may also be used as a second line agent to treat idiopathic urticaria.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HMDB0015273
     RDKit          3D
Doxepin
 42 44  0  0  0  0  0  0  0  0999 V2000
    4.1440   -0.4266    0.5211 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1596   -0.9004   -0.4219 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7657   -1.9014   -1.2451 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6317    0.1573   -1.2255 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7769    1.1010   -0.3098 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7312    0.2345    0.2263 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5541    0.3062    0.2732 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3104   -0.8135    0.9086 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6396   -1.3495    1.9444 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1447   -2.4224    2.6677 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3616   -2.9054    2.2721 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0667   -2.3695    1.2130 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5480   -1.2987    0.5008 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4737   -0.9077   -0.5750 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2256    0.2937   -1.2481 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4866    1.4371   -0.9708 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0180    2.6146   -1.4379 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3619    3.8094   -1.2067 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1739    3.7686   -0.4985 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6074    2.6169   -0.0130 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2792    1.4505   -0.2622 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6229    0.4858    0.0638 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.9015   -1.2235    0.6741 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.6137   -0.1631    1.4643 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.2016   -2.6790   -0.5859 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.5997   -1.4512   -1.8033 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.0625   -2.4211   -1.9246 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.3601    0.7396   -1.7941 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.9098   -0.2872   -1.9406 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.4080    1.8267   -1.0623 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.4269    1.6066    0.3948 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.1663   -0.6909    0.6825 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3065   -0.9209    2.2288 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6131   -2.8590    3.4981 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7870   -3.7443    2.8160 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0341   -2.7844    0.9300 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5316   -1.7731   -1.3155 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5086   -0.8524   -0.1612 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9448    2.6405   -1.9878 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7750    4.7544   -1.5756 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6530    4.6972   -0.3115 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3098    2.6043    0.5973 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  2  3
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21  7  1  0
 13  8  1  0
 21 16  1  0
  1 22  1  0
  1 23  1  0
  1 24  1  0
  3 25  1  0
  3 26  1  0
  3 27  1  0
  4 28  1  0
  4 29  1  0
  5 30  1  0
  5 31  1  0
  6 32  1  0
  9 33  1  0
 10 34  1  0
 11 35  1  0
 12 36  1  0
 14 37  1  0
 14 38  1  0
 17 39  1  0
 18 40  1  0
 19 41  1  0
 20 42  1  0
M  END


  Mrv0541 04191212172D          

 22 24  0  0  0  0            999 V2000
    0.0000    0.0000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7433    0.3580    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7433    0.3580    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9268    1.1623    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3480   -0.2032    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9269    1.1623    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3481   -0.2032    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -1.2375    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4125    1.8073    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7152    1.4055    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1364    0.0400    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4125    1.8073    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.7153    1.4055    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1364    0.0400    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7145   -2.0625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3200    0.8443    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3200    0.8443    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4290   -2.4750    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.1434   -2.0625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4290   -3.3000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -0.8250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7145   -1.2375    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  3  1  0  0  0  0
  1 21  2  0  0  0  0
  2  4  1  0  0  0  0
  2  5  2  0  0  0  0
  3  6  1  0  0  0  0
  3  7  2  0  0  0  0
 21  8  1  0  0  0  0
  4  9  1  0  0  0  0
  4 10  2  0  0  0  0
  5 11  1  0  0  0  0
  6 12  1  0  0  0  0
  6 13  2  0  0  0  0
  7 14  1  0  0  0  0
  8 15  1  0  0  0  0
 10 16  1  0  0  0  0
 13 17  1  0  0  0  0
 15 18  1  0  0  0  0
 18 19  1  0  0  0  0
 18 20  1  0  0  0  0
  9 12  1  0  0  0  0
 11 16  2  0  0  0  0
 14 17  2  0  0  0  0
 21 22  1  4  0  0  0
M  END
> <DATABASE_ID>
HMDB0015273

> <DATABASE_NAME>
hmdb

> <SMILES>
[H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12

> <INCHI_IDENTIFIER>
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

> <INCHI_KEY>
ODQWQRRAPPTVAG-UHFFFAOYSA-N

> <FORMULA>
C19H21NO

> <MOLECULAR_WEIGHT>
279.3761

> <EXACT_MASS>
279.162314299

> <JCHEM_ACCEPTOR_COUNT>
2

> <JCHEM_AVERAGE_POLARIZABILITY>
32.471370833777634

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
0

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
1

> <JCHEM_IUPAC>
dimethyl(3-{9-oxatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine

> <ALOGPS_LOGP>
4.08

> <JCHEM_LOGP>
3.8399740746666673

> <ALOGPS_LOGS>
-3.94

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
3

> <JCHEM_PHYSIOLOGICAL_CHARGE>
1

> <JCHEM_PKA_STRONGEST_BASIC>
9.760738298749509

> <JCHEM_POLAR_SURFACE_AREA>
12.47

> <JCHEM_REFRACTIVITY>
98.24480000000003

> <JCHEM_ROTATABLE_BOND_COUNT>
3

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
3.19e-02 g/l

> <JCHEM_TRADITIONAL_IUPAC>
doxepin

> <JCHEM_VEBER_RULE>
1

$$$$

HMDB0015273
     RDKit          3D
Doxepin
 42 44  0  0  0  0  0  0  0  0999 V2000
    4.1440   -0.4266    0.5211 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1596   -0.9004   -0.4219 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7657   -1.9014   -1.2451 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6317    0.1573   -1.2255 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7769    1.1010   -0.3098 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7312    0.2345    0.2263 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5541    0.3062    0.2732 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3104   -0.8135    0.9086 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6396   -1.3495    1.9444 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1447   -2.4224    2.6677 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3616   -2.9054    2.2721 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0667   -2.3695    1.2130 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5480   -1.2987    0.5008 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4737   -0.9077   -0.5750 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2256    0.2937   -1.2481 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4866    1.4371   -0.9708 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0180    2.6146   -1.4379 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3619    3.8094   -1.2067 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1739    3.7686   -0.4985 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6074    2.6169   -0.0130 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2792    1.4505   -0.2622 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6229    0.4858    0.0638 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.9015   -1.2235    0.6741 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.6137   -0.1631    1.4643 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.2016   -2.6790   -0.5859 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.5997   -1.4512   -1.8033 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.0625   -2.4211   -1.9246 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.3601    0.7396   -1.7941 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.9098   -0.2872   -1.9406 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.4080    1.8267   -1.0623 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.4269    1.6066    0.3948 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.1663   -0.6909    0.6825 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3065   -0.9209    2.2288 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6131   -2.8590    3.4981 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7870   -3.7443    2.8160 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0341   -2.7844    0.9300 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5316   -1.7731   -1.3155 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5086   -0.8524   -0.1612 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9448    2.6405   -1.9878 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7750    4.7544   -1.5756 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6530    4.6972   -0.3115 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3098    2.6043    0.5973 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  2  3
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21  7  1  0
 13  8  1  0
 21 16  1  0
  1 22  1  0
  1 23  1  0
  1 24  1  0
  3 25  1  0
  3 26  1  0
  3 27  1  0
  4 28  1  0
  4 29  1  0
  5 30  1  0
  5 31  1  0
  6 32  1  0
  9 33  1  0
 10 34  1  0
 11 35  1  0
 12 36  1  0
 14 37  1  0
 14 38  1  0
 17 39  1  0
 18 40  1  0
 19 41  1  0
 20 42  1  0
M  END

HEADER    PROTEIN                                 19-APR-12   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   19-APR-12         0                                  
HETATM    1  C   UNK     0       0.000   0.000   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0      -1.387   0.668   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0       1.387   0.668   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0      -1.730   2.170   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0      -2.516  -0.379   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0       1.730   2.170   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0       2.516  -0.379   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0       1.334  -2.310   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0      -0.770   3.374   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0      -3.202   2.624   0.000  0.00  0.00           C+0
HETATM   11  C   UNK     0      -3.988   0.075   0.000  0.00  0.00           C+0
HETATM   12  O   UNK     0       0.770   3.374   0.000  0.00  0.00           O+0
HETATM   13  C   UNK     0       3.202   2.624   0.000  0.00  0.00           C+0
HETATM   14  C   UNK     0       3.988   0.075   0.000  0.00  0.00           C+0
HETATM   15  C   UNK     0       1.334  -3.850   0.000  0.00  0.00           C+0
HETATM   16  C   UNK     0      -4.331   1.576   0.000  0.00  0.00           C+0
HETATM   17  C   UNK     0       4.331   1.576   0.000  0.00  0.00           C+0
HETATM   18  N   UNK     0       2.667  -4.620   0.000  0.00  0.00           N+0
HETATM   19  C   UNK     0       4.001  -3.850   0.000  0.00  0.00           C+0
HETATM   20  C   UNK     0       2.667  -6.160   0.000  0.00  0.00           C+0
HETATM   21  C   UNK     0       0.000  -1.540   0.000  0.00  0.00           C+0
HETATM   22  H   UNK     0      -1.334  -2.310   0.000  0.00  0.00           H+0
CONECT    1    2    3   21                                                  
CONECT    2    1    4    5                                                  
CONECT    3    1    6    7                                                  
CONECT    4    2    9   10                                                  
CONECT    5    2   11                                                       
CONECT    6    3   12   13                                                  
CONECT    7    3   14                                                       
CONECT    8   21   15                                                       
CONECT    9    4   12                                                       
CONECT   10    4   16                                                       
CONECT   11    5   16                                                       
CONECT   12    6    9                                                       
CONECT   13    6   17                                                       
CONECT   14    7   17                                                       
CONECT   15    8   18                                                       
CONECT   16   10   11                                                       
CONECT   17   13   14                                                       
CONECT   18   15   19   20                                                  
CONECT   19   18                                                            
CONECT   20   18                                                            
CONECT   21    1    8   22                                                  
CONECT   22   21                                                            
MASTER        0    0    0    0    0    0    0    0   22    0   48    0
END

COMPND    HMDB0015273
HETATM    1  C1  UNL     1       4.144  -0.427   0.521  1.00  0.00           C  
HETATM    2  N1  UNL     1       3.160  -0.900  -0.422  1.00  0.00           N  
HETATM    3  C2  UNL     1       3.766  -1.901  -1.245  1.00  0.00           C  
HETATM    4  C3  UNL     1       2.632   0.157  -1.225  1.00  0.00           C  
HETATM    5  C4  UNL     1       1.777   1.101  -0.310  1.00  0.00           C  
HETATM    6  C5  UNL     1       0.731   0.235   0.226  1.00  0.00           C  
HETATM    7  C6  UNL     1      -0.554   0.306   0.273  1.00  0.00           C  
HETATM    8  C7  UNL     1      -1.310  -0.814   0.909  1.00  0.00           C  
HETATM    9  C8  UNL     1      -0.640  -1.349   1.944  1.00  0.00           C  
HETATM   10  C9  UNL     1      -1.145  -2.422   2.668  1.00  0.00           C  
HETATM   11  C10 UNL     1      -2.362  -2.905   2.272  1.00  0.00           C  
HETATM   12  C11 UNL     1      -3.067  -2.370   1.213  1.00  0.00           C  
HETATM   13  C12 UNL     1      -2.548  -1.299   0.501  1.00  0.00           C  
HETATM   14  C13 UNL     1      -3.474  -0.908  -0.575  1.00  0.00           C  
HETATM   15  O1  UNL     1      -3.226   0.294  -1.248  1.00  0.00           O  
HETATM   16  C14 UNL     1      -2.487   1.437  -0.971  1.00  0.00           C  
HETATM   17  C15 UNL     1      -3.018   2.615  -1.438  1.00  0.00           C  
HETATM   18  C16 UNL     1      -2.362   3.809  -1.207  1.00  0.00           C  
HETATM   19  C17 UNL     1      -1.174   3.769  -0.498  1.00  0.00           C  
HETATM   20  C18 UNL     1      -0.607   2.617  -0.013  1.00  0.00           C  
HETATM   21  C19 UNL     1      -1.279   1.451  -0.262  1.00  0.00           C  
HETATM   22  H1  UNL     1       4.623   0.486   0.064  1.00  0.00           H  
HETATM   23  H2  UNL     1       4.902  -1.223   0.674  1.00  0.00           H  
HETATM   24  H3  UNL     1       3.614  -0.163   1.464  1.00  0.00           H  
HETATM   25  H4  UNL     1       4.202  -2.679  -0.586  1.00  0.00           H  
HETATM   26  H5  UNL     1       4.600  -1.451  -1.803  1.00  0.00           H  
HETATM   27  H6  UNL     1       3.063  -2.421  -1.925  1.00  0.00           H  
HETATM   28  H7  UNL     1       3.360   0.740  -1.794  1.00  0.00           H  
HETATM   29  H8  UNL     1       1.910  -0.287  -1.941  1.00  0.00           H  
HETATM   30  H9  UNL     1       1.408   1.827  -1.062  1.00  0.00           H  
HETATM   31  H10 UNL     1       2.427   1.607   0.395  1.00  0.00           H  
HETATM   32  H11 UNL     1       1.166  -0.691   0.683  1.00  0.00           H  
HETATM   33  H12 UNL     1       0.307  -0.921   2.229  1.00  0.00           H  
HETATM   34  H13 UNL     1      -0.613  -2.859   3.498  1.00  0.00           H  
HETATM   35  H14 UNL     1      -2.787  -3.744   2.816  1.00  0.00           H  
HETATM   36  H15 UNL     1      -4.034  -2.784   0.930  1.00  0.00           H  
HETATM   37  H16 UNL     1      -3.532  -1.773  -1.315  1.00  0.00           H  
HETATM   38  H17 UNL     1      -4.509  -0.852  -0.161  1.00  0.00           H  
HETATM   39  H18 UNL     1      -3.945   2.640  -1.988  1.00  0.00           H  
HETATM   40  H19 UNL     1      -2.775   4.754  -1.576  1.00  0.00           H  
HETATM   41  H20 UNL     1      -0.653   4.697  -0.312  1.00  0.00           H  
HETATM   42  H21 UNL     1       0.310   2.604   0.597  1.00  0.00           H  
CONECT    1    2   22   23   24
CONECT    2    3    4
CONECT    3   25   26   27
CONECT    4    5   28   29
CONECT    5    6   30   31
CONECT    6    7    7   32
CONECT    7    8   21
CONECT    8    9    9   13
CONECT    9   10   33
CONECT   10   11   11   34
CONECT   11   12   35
CONECT   12   13   13   36
CONECT   13   14
CONECT   14   15   37   38
CONECT   15   16
CONECT   16   17   17   21
CONECT   17   18   39
CONECT   18   19   19   40
CONECT   19   20   41
CONECT   20   21   21   42
END

HMDB0015273
     RDKit          3D
Doxepin
 42 44  0  0  0  0  0  0  0  0999 V2000
    4.1440   -0.4266    0.5211 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1596   -0.9004   -0.4219 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7657   -1.9014   -1.2451 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6317    0.1573   -1.2255 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7769    1.1010   -0.3098 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7312    0.2345    0.2263 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5541    0.3062    0.2732 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3104   -0.8135    0.9086 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6396   -1.3495    1.9444 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1447   -2.4224    2.6677 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3616   -2.9054    2.2721 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0667   -2.3695    1.2130 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5480   -1.2987    0.5008 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4737   -0.9077   -0.5750 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2256    0.2937   -1.2481 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4866    1.4371   -0.9708 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0180    2.6146   -1.4379 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3619    3.8094   -1.2067 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1739    3.7686   -0.4985 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6074    2.6169   -0.0130 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2792    1.4505   -0.2622 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6229    0.4858    0.0638 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.9015   -1.2235    0.6741 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.6137   -0.1631    1.4643 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.2016   -2.6790   -0.5859 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.5997   -1.4512   -1.8033 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.0625   -2.4211   -1.9246 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.3601    0.7396   -1.7941 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.9098   -0.2872   -1.9406 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.4080    1.8267   -1.0623 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.4269    1.6066    0.3948 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.1663   -0.6909    0.6825 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3065   -0.9209    2.2288 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6131   -2.8590    3.4981 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7870   -3.7443    2.8160 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0341   -2.7844    0.9300 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5316   -1.7731   -1.3155 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5086   -0.8524   -0.1612 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9448    2.6405   -1.9878 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7750    4.7544   -1.5756 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6530    4.6972   -0.3115 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3098    2.6043    0.5973 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  2  3
  7  8  1  0
  8  9  2  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  1  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 20  1  0
 20 21  2  0
 21  7  1  0
 13  8  1  0
 21 16  1  0
  1 22  1  0
  1 23  1  0
  1 24  1  0
  3 25  1  0
  3 26  1  0
  3 27  1  0
  4 28  1  0
  4 29  1  0
  5 30  1  0
  5 31  1  0
  6 32  1  0
  9 33  1  0
 10 34  1  0
 11 35  1  0
 12 36  1  0
 14 37  1  0
 14 38  1  0
 17 39  1  0
 18 40  1  0
 19 41  1  0
 20 42  1  0
M  END

View in JSmol View Stereo Labels

Synonyms

Value	Source
3-Dibenz[b,e]oxepin-11(6H)-ylidene-N,N-dimethyl-1-propanamine	ChEBI
Sinequan	Kegg
Doxepine	HMDB
Doxepia	HMDB
Xepin	HMDB
Apo-doxepin	HMDB
Aponal	HMDB
Desidox	HMDB
Espadox	HMDB
Quitaxon	HMDB
Deptran	HMDB
Doneurin	HMDB
Doxepin RPH	HMDB
Novo doxepin	HMDB
Novo-doxepin	HMDB
Sinquan	HMDB
Apo doxepin	HMDB
ApoDoxepin	HMDB
Doxepin hydrochloride	HMDB
Doxepin hydrochloride, cis-trans isomer mixture (approximately 1:5)	HMDB
Doxepin beta	HMDB
Doxepin-RPH	HMDB
Hydrochloride, doxepin	HMDB
Mareen	HMDB
Prudoxin	HMDB
Zonalon	HMDB

Chemical Formula

C₁₉H₂₁NO

Average Molecular Weight

279.3761

Monoisotopic Molecular Weight

279.162314299

IUPAC Name

dimethyl(3-{9-oxatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine

Traditional Name

doxepin

CAS Registry Number

1668-19-5

SMILES

[H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12

InChI Identifier

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

InChI Key

ODQWQRRAPPTVAG-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as dibenzoxepines. Dibenzoxepines are compounds containing a dibenzoxepine moiety, which consists of two benzene connected by an oxazepine ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzoxepines

Sub Class

Dibenzoxepines

Direct Parent

Dibenzoxepines

Alternative Parents

Substituents

Dibenzoxepine
Alkyl aryl ether
Benzenoid
Tertiary aliphatic amine
Tertiary amine
Oxacycle
Ether
Organic nitrogen compound
Organic oxygen compound
Organopnictogen compound
Hydrocarbon derivative
Organooxygen compound
Organonitrogen compound
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

tertiary amino compound (CHEBI:4710 )
dibenzooxepine (CHEBI:4710 )

Ontology

Not Available

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	184 - 186 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	0.032 g/L	Not Available
LogP	4	Not Available

Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct Type	Data Source	CCS Value (Å²)	Reference
[M+H]+	CBM	164.3	30932474

Predicted Molecular Properties

Property	Value	Source
Water Solubility	0.032 g/L	ALOGPS
logP	4.08	ALOGPS
logP	3.84	ChemAxon
logS	-3.9	ALOGPS
pKa (Strongest Basic)	9.76	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	12.47 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	98.24 m³·mol⁻¹	ChemAxon
Polarizability	32.47 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DarkChem	[M+H]+	166.673	31661259
DarkChem	[M-H]-	167.493	31661259
DeepCCS	[M-2H]-	197.38	30932474
DeepCCS	[M+Na]+	172.945	30932474
AllCCS	[M+H]+	165.9	32859911
AllCCS	[M+H-H2O]+	162.3	32859911
AllCCS	[M+NH4]+	169.3	32859911
AllCCS	[M+Na]+	170.2	32859911
AllCCS	[M-H]-	175.0	32859911
AllCCS	[M+Na-2H]-	174.6	32859911
AllCCS	[M+HCOO]-	174.3	32859911

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Doxepin	[H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12	3259.8	Standard polar	33892256
Doxepin	[H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12	2221.2	Standard non polar	33892256
Doxepin	[H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12	2193.9	Semi standard non polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - Doxepin GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-9040000000-78105c767b4d9f9da309	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Doxepin GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-001i-0090000000-c6d70f4744a166243d9c	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-001i-1290000000-843ca75cae9c06d5a947	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-0a4i-3940000000-053eb0b8a655ffc47644	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-0a4i-3920000000-1decbf30162661f4429b	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-0a4i-4920000000-7a9368d04bc38800e87e	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-05ox-4920000000-e6f843926675f1d98789	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-016r-4910000000-1ea8272c7a2859f70a82	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-014i-4910000000-567d6be4466beea7456e	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin LC-ESI-QFT , positive-QTOF	splash10-014r-4900000000-ce29d6e3479d635e3995	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin 30V, Positive-QTOF	splash10-001i-1290000000-d73d7b0c1892f5c68294	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin 15V, Positive-QTOF	splash10-001i-0090000000-453ff45039168ca55cdc	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin 45V, Positive-QTOF	splash10-0a4i-3930000000-a94555ab8999be86527b	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin 60V, Positive-QTOF	splash10-0a4i-3920000000-629459bf098d842e5019	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin 75V, Positive-QTOF	splash10-0a4i-4920000000-c319724e3d8f70aa0da6	2021-09-20	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Doxepin 90V, Positive-QTOF	splash10-05ox-4920000000-33ba3df435da630b3b6f	2021-09-20	HMDB team, MONA	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 10V, Positive-QTOF	splash10-001i-0090000000-a5d3e40d1ca3f87717f1	2017-07-26	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 20V, Positive-QTOF	splash10-001r-2290000000-55156fc7eb59cbc61e49	2017-07-26	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 40V, Positive-QTOF	splash10-0006-9860000000-9086c4a1d64823c60794	2017-07-26	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 10V, Negative-QTOF	splash10-004i-0090000000-a0381cdf59d12afbae2f	2017-07-26	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 20V, Negative-QTOF	splash10-004i-1090000000-770ec6796dd691fe0b27	2017-07-26	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 40V, Negative-QTOF	splash10-0006-8190000000-fc256459fbcf06ebaa2f	2017-07-26	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 10V, Positive-QTOF	splash10-001i-0090000000-5f778b4cfdc4eca13b49	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 20V, Positive-QTOF	splash10-053r-3090000000-9fe0cb253b245b70dfad	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 40V, Positive-QTOF	splash10-0a4i-9540000000-e3859c456dfc4c6641b0	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Doxepin 10V, Negative-QTOF	splash10-004i-0090000000-54d7e5064f0ebcb20f4d	2021-10-11	Wishart Lab	View Spectrum

Biological Properties

Cellular Locations

Extracellular
Membrane

Biospecimen Locations

Blood
Urine

Tissue Locations

Not Available

Pathways

Name	SMPDB/PathBank	KEGG
Doxepin Metabolism Pathway		Not Available
Doxepin H1-Antihistamine Action		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB01142	21059682	details
Urine	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB01142	21059682	details

Abnormal Concentrations

Not Available

Predicted Concentrations

Biospecimen	Value	Original age	Original sex	Original condition	Comments
Blood	0.000 uM	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities
Blood	0.000 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB01142

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

580850

KEGG Compound ID

C06971

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Doxepin

METLIN ID

Not Available

PubChem Compound

667468

PDB ID

Not Available

ChEBI ID

4710

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J: Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct;12(7):571-80. [PubMed:12360109 ]
Virtanen R, Iisalo E, Irjala K: Protein binding of doxepin and desmethyldoxepin. Acta Pharmacol Toxicol (Copenh). 1982 Aug;51(2):159-64. [PubMed:7113722 ]
Virtanen R, Scheinin M, Iisalo E: Single dose pharmacokinetics of doxepin in healthy volunteers. Acta Pharmacol Toxicol (Copenh). 1980 Nov;47(5):371-6. [PubMed:7293791 ]
Negro-Alvarez JM, Carreno-Rojo A, Funes-Vera E, Garcia-Canovas A, Abellan-Aleman AF, Rubio del Barrio R: Pharmacologic therapy for urticaria. Allergol Immunopathol (Madr). 1997 Jan-Feb;25(1):36-51. [PubMed:9111875 ]
Sansone RA, Sansone LA: Pain, pain, go away: antidepressants and pain management. Psychiatry (Edgmont). 2008 Dec;5(12):16-9. [PubMed:19724772 ]

Only showing the first 10 proteins. There are 25 proteins in total.

Show all enzymes and transporters

Enzymes

Enzyme Details

1. Cytochrome P450 2C9

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular weight:: 55627.365

References

Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J: Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct;12(7):571-80. [PubMed:12360109 ]
Hartter S, Tybring G, Friedberg T, Weigmann H, Hiemke C: The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharm Res. 2002 Jul;19(7):1034-7. [PubMed:12180536 ]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Enzyme Details

2. Cytochrome P450 2C19

General function:: Involved in monooxygenase activity
Specific function:: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:: CYP2C19
Uniprot ID:: P33261
Molecular weight:: 55944.565

References

Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J: Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct;12(7):571-80. [PubMed:12360109 ]
Hartter S, Tybring G, Friedberg T, Weigmann H, Hiemke C: The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharm Res. 2002 Jul;19(7):1034-7. [PubMed:12180536 ]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Enzyme Details

3. Cytochrome P450 2D6

General function:: Involved in monooxygenase activity
Specific function:: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:: CYP2D6
Uniprot ID:: P10635
Molecular weight:: 55768.94

References

Szewczuk-Boguslawska M, Kiejna A, Beszlej JA, Orzechowska-Juzwenko K, Milejski P: Doxepin inhibits CYP2D6 activity in vivo. Pol J Pharmacol. 2004 Jul-Aug;56(4):491-4. [PubMed:15520506 ]
Grasmader K, Verwohlt PL, Rietschel M, Dragicevic A, Muller M, Hiemke C, Freymann N, Zobel A, Maier W, Rao ML: Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol. 2004 Jul;60(5):329-36. Epub 2004 May 28. [PubMed:15168101 ]
Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J: Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct;12(7):571-80. [PubMed:12360109 ]
Haritos VS, Ghabrial H, Ahokas JT, Ching MS: Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin. Pharmacogenetics. 2000 Oct;10(7):591-603. [PubMed:11037801 ]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Enzyme Details

4. Cytochrome P450 1A2

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:: CYP1A2
Uniprot ID:: P05177
Molecular weight:: 58406.915

References

Hartter S, Tybring G, Friedberg T, Weigmann H, Hiemke C: The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharm Res. 2002 Jul;19(7):1034-7. [PubMed:12180536 ]
Haritos VS, Ghabrial H, Ahokas JT, Ching MS: Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin. Pharmacogenetics. 2000 Oct;10(7):591-603. [PubMed:11037801 ]
Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Enzyme Details

5. Alpha-2A adrenergic receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:: ADRA2A
Uniprot ID:: P08913
Molecular weight:: 48956.3

References

Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217 ]

Enzyme Details

6. Alpha-2B adrenergic receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol
Gene Name:: ADRA2B
Uniprot ID:: P18089
Molecular weight:: 49953.1

References

Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217 ]

Enzyme Details

7. D(2) dopamine receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:: DRD2
Uniprot ID:: P14416
Molecular weight:: 50618.9

References

Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217 ]
Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed:6086881 ]

Enzyme Details

8. Histamine H2 receptor

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway
Gene Name:: HRH2
Uniprot ID:: P25021
Molecular weight:: 40097.7

References

Beil W, Hannemann H, Sewing KF: Interaction of antidepressants and neuroleptics with histamine stimulated parietal cell adenylate cyclase and H+ secretion. Pharmacology. 1988;36(3):198-203. [PubMed:2897127 ]
Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [PubMed:2141000 ]

Enzyme Details

9. 5-hydroxytryptamine receptor 2B

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system
Gene Name:: HTR2B
Uniprot ID:: P41595
Molecular weight:: 54297.4

References

Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217 ]
Maj J, Gancarczyk L, Gorszczyk L, Rawlow A: Doxepin as a blocker of central serotonin receptors. Pharmakopsychiatr Neuropsychopharmakol. 1977 Dec;10(6):318-24. [PubMed:309138 ]

Enzyme Details

10. 5-hydroxytryptamine receptor 1A

General function:: Involved in G-protein coupled receptor protein signaling pathway
Specific function:: This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity
Gene Name:: HTR1A
Uniprot ID:: P08908
Molecular weight:: 46106.3

References

Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217 ]
Maj J, Gancarczyk L, Gorszczyk L, Rawlow A: Doxepin as a blocker of central serotonin receptors. Pharmakopsychiatr Neuropsychopharmakol. 1977 Dec;10(6):318-24. [PubMed:309138 ]

Transporters

Enzyme Details

1. Multidrug resistance protein 1

General function:: Involved in ATP binding
Specific function:: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:: ABCB1
Uniprot ID:: P08183
Molecular weight:: 141477.3

References

Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [PubMed:12438524 ]

Enzyme Details

2. Sodium-dependent noradrenaline transporter

General function:: Involved in neurotransmitter:sodium symporter activity
Specific function:: Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:: SLC6A2
Uniprot ID:: P23975
Molecular weight:: 69331.42

References

Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821 ]
Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [PubMed:19179941 ]

Enzyme Details

3. Sodium-dependent serotonin transporter

General function:: Involved in neurotransmitter:sodium symporter activity
Specific function:: Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:: SLC6A4
Uniprot ID:: P31645
Molecular weight:: 70324.165

References

Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821 ]
Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [PubMed:19179941 ]

Only showing the first 10 proteins. There are 25 proteins in total.

Show all enzymes and transporters

Showing metabocard for Doxepin (HMDB0015273)

MOL for HMDB0015273 (Doxepin)

3D MOL for HMDB0015273 (Doxepin)

3D SDF for HMDB0015273 (Doxepin)

3D-SDF for HMDB0015273 (Doxepin)

PDB for HMDB0015273 (Doxepin)

3D PDB for HMDB0015273 (Doxepin)

SMILES for HMDB0015273 (Doxepin)

INCHI for HMDB0015273 (Doxepin)

Structure for HMDB0015273 (Doxepin)

3D Structure for HMDB0015273 (Doxepin)

Experimental Collision Cross Sections

Predicted Collision Cross Sections

Predicted Kovats Retention Indices

Underivatized

GC-MS Spectra

MS/MS Spectra

Enzymes

References

References

References

References

References

References

References

References

References

References

Transporters

References

References

References