Repositioning Candidate Details
| Candidate ID: | R0423 |
| Source ID: | DB01142 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Doxepin |
| Synonyms: | Doxepin |
| Molecular Formula: | C19H21NO |
| SMILES: | [H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12 |
| Structure: |
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| DrugBank Description: | Doxepin is a psychotropic agent with antidepressant and anxiolytic properties. It is a tertiary amine that can be presented as (E) and (Z) stereoisomers with the (Z) stereoisomer corresponding to . Doxepin commonly produces a 5:1 (E):(Z) racemic mixture. In a strict sense, doxepin is not a tricyclic antidepressant but it is commonly associated with the class since it shares a lot of properties with members of the drug family including , , , , , and . Doxepin was developed by Pfizer and FDA approved in 1969 as an antidepressant. However, in 2010 it was approved for the treatment of insomnia. The latter indication was presented by Pernix Therapeutics. |
| CAS Number: | 1668-19-5 |
| Molecular Weight: | 279.3761 |
| DrugBank Indication: | Oral doxepin is approved for the following indications: - Treatment of depression and/or anxiety. - Treatment of depression and/or anxiety associated with different conditions, including alcoholism, organic disease and manic-depressive disorders. - Treatment of psychotic depressive disorders with associated anxiety. - Treatment of involutional depression. - Treatment of manic-depressive disorder. - Treatment of insomnia characterized by difficulties with sleep maintenance. Topical doxepin is also approved for short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis, pruritus or lichen simplex chronicus. Off-label, doxepin is used topically for the management of neuropathic pain. Depression is a common medical illness that causes feelings of sadness and or loss of interest in prior enjoyable activities. This condition can lead to emotional and physical disturbances that can decrease the ability of a person to function in a regular environment. Anxiety is a normal reaction of the body towards a normal danger. When the anxious state is exacerbated or appears on situations without danger, it is defined as an anxiety disorder. This disorders can appear in different forms such as phobias, panic, obsessive-compulsive disorder and post-traumatic stress disorder. Insomnia is a sleep disorder that directly affects the quality of life of the individual. It is characterized by the complication either to fall asleep or to stay asleep. This condition can be occasional or chronic. Pruritus is defined as an unpleasant skin reaction that provokes the urge to scratch. It can be localized or generalized and it can appear in an acute or chronic manner. Neuropathic pain occurs due to the damage or dysfunction of the peripheral or central nervous system rather than stimulation of the pain receptors. |
| DrugBank Pharmacology: | Similar to other tricyclic antidepressants, doxepin was shown, in preclinical trials, to decrease the electrical activity of the brain, prolong the hexobarbital-induced sleep and block avoidance behavior without affecting the conditioned emotional response. At high doses, it also produces symptoms of central nervous system depression. Doxepin is known to cause antidepressant, sedative, and anticholinergic effects. At high doses, its anticholinergic and antiadrenergic properties are the most prevalent which limit its efficacy. These effects are observed at high doses where its affinity for H1 histamine receptor is lost and its binding to other receptors is observed. The maximal antidepressive effects of doxepin are present around two weeks following initiation of therapy. However, the sedative effects of doxepin, usually used for the treatment of insomnia or anxiety, are observed immediately after administration. |
| DrugBank MoA: | Doxepin exact mechanism of action is not very clear. However, doxepin is known to be a selective histamine H1 receptor blocker. This effect on histamine receptors indicates effectiveness in skin conditions. Breaking its function according to the different effect, doxepin's antidepressive action is primarily associated with the inhibition of the central nervous system biogenic amine reuptake; more specifically, norepinephrine and serotonin at synaptic nerve terminals. This effect increases the level of monoamines in the synaptic site which in order increases the activity at the post-synaptic neuron receptor sites. It has been suggested that doxepin also desensitizes both serotonin 1A receptors and beta-adrenergic receptors. It is known that the lack of dopamine transporters in the frontal cortex and the transmission of dopamine in this region is largely inactivated by the effect of norepinephrine reuptake. Hence, doxepin action on the frontal cortex is suggested to increase dopamine neurotransmission in this area. |
| Targets: | Histamine H1 receptor antagonist; Histamine H2 receptor antagonist; Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 2B antagonist; 5-hydroxytryptamine receptor 2C antagonist; Muscarinic acetylcholine receptor M1 antagonist; Muscarinic acetylcholine receptor M2 antagonist; Muscarinic acetylcholine receptor M3 antagonist; Muscarinic acetylcholine receptor M4 antagonist; Muscarinic acetylcholine receptor M5 antagonist; Alpha-1A adrenergic receptor antagonist; Alpha-1B adrenergic receptor antagonist; Alpha-1D adrenergic receptor antagonist; 5-hydroxytryptamine receptor 1A antagonist; 5-hydroxytryptamine receptor 6 binder; Histamine H4 receptor binder; Potassium voltage-gated channel subfamily H member 2 inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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