| Candidate ID: | R0113 |
| Source ID: | DB00321 |
| Source Type: | approved |
| Compound Type: |
small molecule
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| Compound Name: |
Amitriptyline
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| Synonyms: |
10,11-dihydro-5-(γ-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene; 10,11-dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-Δ5,γ-propylamine; 3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine; 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine; 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatriene; 5-(3-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene; 5-(γ-dimethylaminopropylidene)-5H-dibenzo[a,d][1,4]cycloheptadiene; Amitriptyline
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| Molecular Formula: |
C20H23N
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| SMILES: |
CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12
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| Structure: |
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| DrugBank Description: |
Amitriptyline hydrochloride, also known as _Elavil_, is a tricyclic antidepressant (TCA) with analgesic properties, widely used to treat depression and neuropathic pain . It was originally approved by the FDA in 1977 and manufactured by Sandoz .
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| CAS Number: |
50-48-6
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| Molecular Weight: |
277.4033
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| DrugBank Indication: |
This drug in indicated for the following conditions :
Major depressive disorder in adults
Management of neuropathic pain in adults
Prophylactic treatment of chronic tension-type headache (CTTH) in adults
Prophylactic treatment of migraine in adults
Treatment of nocturnal enuresis in children aged 6 years and above when organic pathology, including spina bifida and related disorders, have been excluded and no response has been achieved to all other non-drug and drug treatments, including antispasmodics and vasopressin-related products. This product should only be prescribed by a healthcare professional with expertise in the management of persistent enuresis
Off-label uses: irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation, fibromyalgia, and insomnia
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| DrugBank Pharmacology: |
**Effects in pain and depression**
Amitriptyline is a tricyclic antidepressant and an analgesic. It has anticholinergic and sedative properties .
Clinical studies have shown that oral amitriptyline achieves, at a minimum, good to moderate response in up to 2/3 of patients diagnosed with post-herpetic neuralgia and 3/4 of patients diagnosed with diabetic neuropathic pain, and neurogenic pain syndromes that are frequently unresponsive to narcotic analgesics. Amitriptyline has also shown efficacy in diverse groups of patients with chronic non-malignant pain. There have also been some studies showing efficacy in managing fibromyalgia (an off-label use of this drug) , .
**Cardiovascular and Anticholinergic Effects**
Amitriptyline has strong anticholinergic properties and may cause ECG changes and quinidine-like effects on the heart . Amitriptyline may inhibit ion channels, which are necessary for cardiac repolarization (hERG channels), in the upper micromolar range of therapeutic plasma concentrations. Therefore, amitriptyline may increase the risk for cardiac arrhythmia . Orthostatic hypotension and tachycardia can be a problem in elderly patients receiving this drug at normal doses for depression. There is evidence in the literature that these effects may occur, rarely, at the lower dosages utilized in the treatment of pain. As with any other tricyclic antidepressant agent, increased glucose levels can occur with amitriptyline .
**Effects on seizure threshold**
This drug also decreases the convulsive threshold and causes alterations in EEG and sleep patterns .
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| DrugBank MoA: |
The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain , . These amines are important in regulating mood. The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (5-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects . This drug counteracts these mechanisms, and this may be the mechanism of amitriptyline in improving depressive symptoms.
Whether its analgesic effects are related to its mood-altering activities or attributable to a different, less obvious pharmacological action (or a combination of both) is unknown .
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| Targets: |
Sodium-dependent noradrenaline transporter inhibitor; Sodium-dependent serotonin transporter inhibitor; 5-hydroxytryptamine receptor 2A antagonist; 5-hydroxytryptamine receptor 1A inhibitor&inducer; Delta-type opioid receptor agonist; Kappa-type opioid receptor agonist; High affinity nerve growth factor receptor agonist&activator; BDNF/NT-3 growth factors receptor agonist; Alpha-1A adrenergic receptor antagonist&inhibitor; Alpha-1D adrenergic receptor antagonist; Alpha-2A adrenergic receptor antagonist&agonist; Histamine H1 receptor antagonist; Potassium voltage-gated channel subfamily KQT member 2 inhibitor; Potassium voltage-gated channel subfamily A member 1 inhibitor; Histamine H2 receptor blocker; Histamine H4 receptor binder; Sigma non-opioid intracellular receptor 1 agonist; 5-hydroxytryptamine receptor 2C antagonist; Alpha-1B adrenergic receptor antagonist; 5-hydroxytryptamine receptor 7 antagonist; 5-hydroxytryptamine receptor 1D binder; Mu-type opioid receptor binder; 5-hydroxytryptamine receptor 1B binder; 5-hydroxytryptamine receptor 6 antagonist; Potassium voltage-gated channel subfamily KQT member 3 inhibitor; 5-hydroxytryptamine receptor 1C antagonist; Muscarinic acetylcholine receptor ligand; HERG human cardiac K+ channel blocker
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| Inclusion Criteria: |
Indication associated
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