Nortriptyline

Nortriptyline is used to treat depression. A level between 50 and 150 ng/mL of nortriptyline in the blood generally corresponds with an antidepressant effect. It is also used off-label for the treatment of panic disorder, ADHD, irritable bowel syndrome, tobacco-cessation, migraine prophylaxis and chronic pain or neuralgia modification, particularly temporomandibular joint disorder. ==Contraindications==

Nortriptyline should not be used in the acute recovery phase after myocardial infarction (heart attack). Closer monitoring is required for those with a history of cardiovascular disease, stroke, glaucoma, or seizures, as well as in persons with hyperthyroidism or receiving thyroid hormones. ==Side effects==

The most common side effects include dry mouth, sedation, constipation, increased appetite, blurred vision and tinnitus. An occasional side effect is a rapid or irregular heartbeat. Alcohol may exacerbate some of its side effects. ==Overdose==

The symptoms and the treatment of an overdose are generally the same as for the other tricyclic antidepressants, including anticholinergic effects, serotonin syndrome and adverse cardiac effects. TCAs, particularly nortriptyline, have a relatively narrow therapeutic index, which increase the chance of an overdose (both accidental and intentional). Symptoms of overdose include: irregular heartbeat, seizures, coma, confusion, hallucination, widened pupils, drowsiness, agitation, fever, low body temperature, stiff muscles and vomiting. ==Interactions==

Excessive consumption of alcohol in combination with nortriptyline therapy may have a potentiating effect, which may lead to the danger of increased suicidal attempts or overdosage, especially in patients with histories of emotional disturbances or suicidal ideation. It may interact with the following drugs: • heart rhythm medications such as flecainide (Tambocor), propafenone (Rhythmol), or quinidine (Cardioquin, Quinidex, Quinaglute) • cimetidine • guanethidine • reserpine ==Pharmacology==

Nortriptyline is a strong norepinephrine reuptake inhibitor and a moderate serotonin reuptake inhibitor. Additionally, nortriptyline inhibits the activity of histamine and acetylcholine. Its pharmacologic profile is as the table shows with (inhibition or antagonism of all sites). Pharmacodynamics Nortriptyline is an active metabolite of amitriptyline by demethylation in the liver. Chemically, it is a secondary amine dibenzocycloheptene and pharmacologically it is classed as a first-generation antidepressant. Nortriptyline may also have a sleep-improving effect due to antagonism of the H1 and 5-HT2A receptors. In the short term, however, nortriptyline may disturb sleep due to its activating effect. In one study, nortriptyline had the highest affinity for the dopamine transporter among the tricyclic antidepressants (KD = 1,140 nM) besides amineptine (a norepinephrine–dopamine reuptake inhibitor), although its affinity for this transporter was still 261- and 63-fold lower than for the norepinephrine and serotonin transporters (KD = 4.37 and 18 nM, respectively). Increased concentrations of nortriptyline may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drug's efficacy. Individuals can be categorized into different types of CYP2D6 metabolizers depending on which genetic variations they carry. These metabolizer types include poor, intermediate, extensive, and ultrarapid metabolizers. Most individuals (about 77–92%) are extensive metabolizers, ==Chemistry==

Nortriptyline is a tricyclic compound, specifically a dibenzocycloheptadiene, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzocycloheptadiene tricyclic antidepressants include amitriptyline (N-methylnortriptyline), protriptyline, and butriptyline. Nortriptyline is a secondary amine tricyclic antidepressant, with its N-methylated parent amitriptyline being a tertiary amine. Other secondary amine tricyclic antidepressants include desipramine and protriptyline. The chemical name of nortriptyline is 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine and its free base form has a chemical formula of C19H21N1 with a molecular weight of 263.384 g/mol. ==History==

Nortriptyline was developed by Geigy. It first appeared in the literature in 1962 and was patented the same year. ==Society and culture==

Generic names Nortriptyline is the generic name of the drug and its , , and , while nortriptyline hydrochloride is its , , , and . Its generic name in Spanish and Italian and its are nortriptilina, in German is nortriptylin, and in Latin is nortriptylinum. Brand names Brand names of nortriptyline include Allegron, Aventyl, Noritren, Norpress, Nortrilen, Norventyl, Norzepine, Pamelor, and Sensival, among many others. == Research ==

Although not approved by the US Food and Drug Administration (FDA) for neuropathic pain, randomized controlled trials have demonstrated the effectiveness of tricyclic antidepressants for the treatment of this condition in both depressed and non-depressed individuals. In 2010, an evidence-based guideline sponsored by the International Association for the Study of Pain recommended nortriptyline as a first-line medication for neuropathic pain. However, in a 2015 Cochrane systematic review the authors did not recommend nortriptyline as a first-line agent for neuropathic pain. It may be effective in the treatment of tobacco-cessation. ==References==