nortriptyline

ノルトリプチリン 　

WordNet

1. a tricyclic antidepressant drug (trade name Pamelor) used along with psychotherapy to treat dysthymic depression; may interact dangerously if taken with other drugs (同)Pamelor

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/20 19:50:35」(JST)

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Nortriptyline

Systematic (IUPAC) name
3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine
Clinical data
Trade names	Aventyl
AHFS/Drugs.com	monograph
MedlinePlus	a682620
Pregnancy cat.	C (AU)
Legal status	Prescription Only (S4) (AU) ℞-only (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	High
Metabolism	Hepatic
Half-life	16 and 90 hours
Excretion	Renal
Identifiers
CAS number	72-69-5 Y 894-71-3 (hydrochloride)
ATC code	N06AA10
PubChem	CID 4543
IUPHAR ligand	2404
DrugBank	DB00540
ChemSpider	4384 Y
UNII	BL03SY4LXB Y
KEGG	D08288 Y
ChEBI	CHEBI:7640 Y
ChEMBL	CHEMBL445 Y
Chemical data
Formula	C19H21N
Mol. mass	263.38 g/mol
SMILES c3cc2c(/C(c1c(cccc1)CC2)=C/CCNC)cc3
InChI InChI=1S/C19H21N/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19/h2-5,7-11,20H,6,12-14H2,1H3 Y Key:PHVGLTMQBUFIQQ-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Nortriptyline is a second-generation tricyclic antidepressant (TCA) marketed as the hydrochloride salt under the trade names Sensoval, Aventyl, Pamelor, Norpress, Allegron, Noritren and Nortrilen. It is used in the treatment of major depression and childhood nocturnal enuresis (bedwetting). In addition, it is sometimes used for chronic illnesses such as chronic fatigue syndrome^{[citation needed]}, chronic pain and migraine, and labile affect in some neurological conditions.

Clinical pharmacology

Nortriptyline is an active metabolite of amitriptyline that is demethylated in the liver. Its pharmacologic profile is as follows:

Receptor/Transporter Protein	Binding Affinity (Ki[nM])	Receptor location and species
SERT	16.5	Human, cloned
NET	4.37	Human, cloned
DAT	3100	Human, cloned
5-HT1A	294	Human, brain
5-HT2A	5	Rat, cloned
5-HT2C	8.5	Rat, cloned
5-HT6	148	Rat, cloned
α1	55	Human, brain
α2	2030	Human, brain
β	>10000	Mammalian, brain
M1	40	Human, cloned
M2	110	Human, cloned
M3	50	Human, cloned
M4	84	Human, cloned
M5	97	Human, cloned
D2	2570	Human, brain
H1	15.1	Human, cloned
Sigma receptor	2000	Guinea pig, brain

These effects account for some therapeutic actions as well as for most side effects such as sedation, hypotension, anticholinergic effects, etc. Nortriptyline may also have a sleep-improving effect due to its affinity for 5HT_2A and histaminergic receptors. In the short run however, nortriptyline may disturb sleep due to its activating effect.

Like other tricyclic antidepressants, nortriptyline also blocks sodium channels, possibly accounting in part for its analgesic action.

In one study of long-term efficacy, nortriptyline showed a higher relapse rate in comparison with phenelzine in individuals being treated for depression, possibly due to the metabolite 10-hydroxynortriptyline being produced. The authors of a review noted that the nortriptyline group had more episodes prior to treatment.

Indications

Nortriptyline is FDA-approved for the treatment of major depression. In the United Kingdom, it may also be used for treating nocturnal enuresis, with courses of treatment lasting no more than three months. It is also used off-label for the treatment of panic disorder, irritable bowel syndrome, migraine prophylaxis and chronic pain or neuralgia modification, particularly temporomandibular joint disorder. It can also aid in quitting smoking, with one study showing a six-month abstinence rate of 14% for subjects receiving nortriptyline compared to 3% for subjects not undergoing pharmacological treatment. Research has been done suggesting it can also reduce symptoms of ADHD.

Neuropathic pain

Although not approved by the FDA for neuropathic pain, a large number of randomized controlled trials have proven the efficacy of tricyclic antidepressants for the treatment of this condition in both depressed and non-depressed individuals. Recently, an evidence-based guideline sponsored by the International Association for the Study of Pain recommends nortriptyline as a first-line medication for neuropathic pain.

Metabolism

Nortriptyline is metabolized in the liver by the hepatic enzyme CYP2D6. Approximately 7-10% of caucasians are poor metabolizers and might experience more adverse effects, so a lower dosage is often necessary in these individuals. Blood levels of nortriptyline should be obtained during long term treatment to avoid toxicity and optimize response.

Dosage

For depression low starting doses are used, increasing as necessary to 75–100 mg (0–50 mg for adolescents and the elderly). Maximum daily dosage is 150 mg.

For the management of nocturnal enuresis lower dosages are used with a maximum period of three months, followed by gradual withdrawal, and a full examination including electrocardiogram required before further courses.

For its off-label use for migraine and headache prophylaxis and treating chronic pain treatment is started at very low 10 mg once at night to minimize side-effects. The dose is then increased every two weeks if required to a maximum of 150 mg.

Dosage availability is 10 mg, 25 mg, 50 mg, and 75 mg capsules (Sandoz/Mallinckrodt Pharm).

Side effects

The most common side effects include dry mouth, sedation, constipation, and increased appetite, mild blurred vision, tinnitus, often euphoria and mania. An occasional side effect is a rapid or irregular heartbeat. Alcohol may exacerbate some of its side effects and should be avoided.

However, the incidence of side effects with nortriptyline is lower than with the first-generation tricyclics (e.g., imipramine (Tofranil), amitriptyline (Elavil)). For this reason it is often used in elder patients instead of other TCAs to reduce side effects and improving patient's compliance.

A study with men has found that treatment with nortriptyline is associated with higher risk of suicidal ideation compared to escitalopram.

Warnings

Closer monitoring is required for those with a history of cardiovascular disease, stroke, glaucoma, or seizures, as well as those that have hyperthyroidism or are receiving thyroid medication.

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.

Contraindications

Nortriptyline should not be used in the acute recovery phase after myocardial infarction (e.g., heart attack). As for all tricyclic antidepressants, concurrent use, or failure to allow a two-week gap with monoamine oxidase inhibitors (MAO inhibitors, e.g., phenelzine, tranylcypromine, etc.) may precipitate hyperpyretic crisis caused by serotonin syndrome or severe convulsions.

Overdose

Main article: Tricyclic antidepressant overdose

The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants, including serotonin syndrome and adverse cardiac effects. As tricyclic antidepressants have a relatively narrow therapeutic index, the likelihood of overdose (both accidental and intentional) is fairly high and should be considered carefully by the prescribing physician prior to patient use.

A nortriptyline overdose should always be considered a medical emergency and can result in death. In the event of a known or suspected overdose, poison control (1-800-222-1222 in the U.S.) or 911 (999 in the U.K.) should be contacted immediately. If no phone services are available the overdose victim should be brought to the nearest hospital as soon as possible.

See also

• Tricyclic antidepressant

References

External links

• Internet Mental Health - Nortriptyline
• Drugs.com - Nortriptyline

UpToDate Contents

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English Journal

• Therapeutic doses of antidepressants are projected not to inhibit human α4β2 nicotinic acetylcholine receptors.

• Weber ML, Hofland CM, Shaffer CL, Flik G, Cremers T, Hurst RS, Rollema H.SourceNeuroscience Research Unit, Worldwide Research & Development, Pfizer Inc., 700 Main Street, Cambridge, MA 02139, USA.
• Neuropharmacology.Neuropharmacology.2013 Sep;72:88-95. doi: 10.1016/j.neuropharm.2013.04.027. Epub 2013 Apr 30.
• Inhibition of central α4β2 nAChRs by antidepressants, proposed to contribute to their clinical efficacy, was assessed for monoamine reuptake inhibitors (amitriptyline, nortriptyline, fluoxetine, sertraline, paroxetine, citalopram) by comparing projected human unbound brain drug concentrations (Cu,
• PMID 23639435

• Interaction of valproic Acid and amitriptyline: analysis of therapeutic drug monitoring data under naturalistic conditions.

• Unterecker S, Burger R, Hohage A, Deckert J, Pfuhlmann B.SourceFrom the Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Germany.
• Journal of clinical psychopharmacology.J Clin Psychopharmacol.2013 Aug;33(4):561-4. doi: 10.1097/JCP.0b013e3182905d42.
• Amitriptyline (AMI) and valproic acid (VPA) are common psychotropic drugs which are frequently used in psychiatry and also administered in neurology or anesthesia in the absence of a psychiatric indication. On the basis of the case of a 73-year-old man with therapy-resistant major depressive episode
• PMID 23775047

• Human UDP-Glucuronosyltransferase (UGT) 2B10 in Drug N-Glucuronidation: Substrate Screening and Comparison with UGT1A3 and UGT1A4.

• Kato Y, Izukawa T, Oda S, Fukami T, Finel M, Yokoi T, Nakajima M.SourceDrug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan. nmiki@p.kanazawa-u.ac.jp.
• Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2013 Jul;41(7):1389-97. doi: 10.1124/dmd.113.051565. Epub 2013 Apr 23.
• Recent observations revealed that human UDP-glucuronosyltransferase (UGT) 2B10 catalyzes N-glucuronidation of amine-containing compounds. Knowledge of the substrate specificity and clinical significance of UGT2B10 is still limited. The purpose of this study was to expand the knowledge of UGT2B10 sub
• PMID 23611809

Japanese Journal

• 肝移植後の重症帯状疱疹に対しトラマドールが有用であった1例

• 吉武 美緒,眞鍋 治彦,久米 克介,加藤 治子,武藤 官大
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• 久米 克介,眞鍋 治彦,武藤 官大 [他],武藤 佑理,眞鍋 祐美子
• 日本ペインクリニック学会誌 22(2), 101-104, 2015
• 悪性リンパ腫および骨髄異形成症治療のため造血幹細胞移植を受けた後に帯状疱疹（herpes zoster：HZ）を発症，その治療中に耐え難い電撃様痛発作を繰り返し，バルプロ酸で痛みが消失した3症例を経験した．症例1は，60歳，男性．悪性リンパ腫に対して臍帯血移植を受けた4カ月後に三叉神経第1枝のHZを発症，15日目より耐え難い電撃様痛発作を繰り返したためノルトリプチリン，ガバペンチンに加えてバルプロ …
• NAID 130005083677

• 薬剤調整を行ったことで修正型電気けいれん療法の効果が改善したうつ病の1症例

• 近藤 年隆,石川 高明,尾関 祐二 [他]
• 精神科 25(4), 461-464, 2014-10
• NAID 40020226231

Related Links

• Nortriptyline - Wikipedia, the free encyclopedia

Nortriptyline is a second-generation tricyclic antidepressant (TCA) marketed as the hydrochloride salt under the trade names Sensoval, Aventyl, Pamelor, Norpress, Allegron, Noritren and Nortrilen. It is used in the treatment of major depression ...

• Nortriptyline - Internet Mental Health

The concurrent use of nortriptyline or other tricyclic antidepressants with a MAO inhibitor is contraindicated. Hyperpyretic crises, severe convulsions, and fatalities have occurred when similar tricyclic antidepressants were used in such ...

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塩酸ノルトリプチリン nortriptyline hydrochloride

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