nortriptyline hydrochloride

• 塩酸ノルトリプチリン

関

nortriptyline

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
2. a complex consisting of an organic base in association with hydrogen chloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/01 21:42:38」(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

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English Journal

• Cost-effectiveness analysis of clinical smoking cessation interventions in Thailand.

• Tosanguan J1, Chaiyakunapruk N2,3,4,5.
• Addiction (Abingdon, England).Addiction.2016 Feb;111(2):340-50. doi: 10.1111/add.13166. Epub 2015 Oct 26.
• AIMS: Clinical smoking cessation interventions have been found typically to be highly cost-effective in many high-income countries. There is a need to extend this to low- and middle-income countries and undertake comparative analyses. This study aimed to estimate the incremental cost-effectiveness r
• PMID 26360507

• Determination of tricyclic antidepressants in biota tissue and environmental waters by liquid chromatography-tandem mass spectrometry.

• Ziarrusta H1, Mijangos L1, Prieto A1, Etxebarria N1,2, Zuloaga O3,4, Olivares M1.
• Analytical and bioanalytical chemistry.Anal Bioanal Chem.2016 Feb;408(4):1205-16. doi: 10.1007/s00216-015-9224-y. Epub 2015 Dec 16.
• This work describes the optimization, validation, and application in real samples of accurate and precise analytical methods to determine tricyclic antidepressants (TCAs), including amitriptyline, nortriptyline, imipramine, and clomipramine in different environmental matrices, such as water (estuary
• PMID 26677016

• Tricyclic and related drugs for nocturnal enuresis in children.

• Caldwell PH1, Sureshkumar P, Wong WC.
• The Cochrane database of systematic reviews.Cochrane Database Syst Rev.2016 Jan 20;1:CD002117. [Epub ahead of print]
• BACKGROUND: Enuresis (bedwetting) affects up to 20% of five year-olds and 2% of adults. Although spontaneous remission often occurs, the social, emotional and psychological costs can be great. Tricyclics have been used to treat enuresis since the 1960s.OBJECTIVES: To assess the effects of tricyclic
• PMID 26789925

Japanese Journal

• Sensitive Extractive Spectrophotometric Methods for the Determination of Nortriptyline Hydrochloride in Pharmaceutical Formulations

• Misiuk Wieslawa,Tykocka Agnieszka
• Chemical & pharmaceutical bulletin 55(12), 1655-1661, 2007-12-01
• … Two simple, sensitive and rapid extractive spectrophotometric methods have been developed for the assay of the antidepressant drug nortriptyline (NOR) hydrochloride in pure form and in different dosage forms. … The methods permit the determination of nortriptyline over a concentration range of 15—100 μg/ml and 5—24 μg/ml with the detection limit of 0.84 μg/ml and 0.32 μg/ml, using Nb-SCN and Fe-SCN, respectively. …
• NAID 110006532104

• フマル酸ケトチフェンによる接触皮膚炎の１例

• 有馬 豪,松永 佳世子,鈴木 加余子,秋田 浩孝,鷲見 康子,川部 美智子
• 皮膚 43(1), 19-23, 2001
• 58歳, 女性. アレルギー性結膜炎のためフサコール<SUP>®</SUP>点眼液を使用中, 両側上下眼瞼に痒みを伴う紅斑が出現した. パッチテストでザジテン<SUP>®</SUP>点眼液及び主成分のフマル酸ケトチフェンに陽性であった. フマル酸ケトチフェンの類似構造物質であるチアプロフェン酸, スプロフェン, 塩酸ノルトリプチリン, …
• NAID 130003844159

• Release of Nortriptyline Hydrochloride from Oil-Water Microemulsions

• Moreno MarcoAntonio,Frutos Paloma,Ballesteros Ma Paloma [他],LASTRES Jose Luis,CASTRO David,,,,,
• Chemical & pharmaceutical bulletin 48(11), 1623-1627, 2000-11-01
• … release of nortriptyline hydrochloride from oil-in-water (o/w) microemulsions (isopropyl myristate as oil, propylene glycol as cosurfactant, polysorbate 80 as surfactant and phosphate buffer, pH 7.4,as the continuous phase) containing increasing concentrations of polyethylene glycol 400,used to facilitate the diffusion of a drug from the inner oily phase of the microemulsion to the outer aqueous phase of such a dispersion system, was studied by determing the permeability constants of the drug through hydrophilic and lipophilic …
• NAID 110003635338

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リンク元	「ノルトリプチリン」
関連記事	「hydrochloride」「nortriptyline」

「ノルトリプチリン」

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nortriptyline

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塩酸ノルトリプチリン nortriptyline hydrochloride

商

ノリトレン、Aventyl, Pamelor

関

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「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド 　

「nortriptyline」

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