Ludiomil

マプロチリン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/03/14 18:06:26」(JST)

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Maprotiline

Clinical data
AHFS/Drugs.com	Monograph
MedlinePlus	a682158
Pregnancy category	US: B3[in US?]
Routes of administration	oral, intramuscular, intravenous (infusion)
ATC code	N06AA21 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	66–70%
Protein binding	88%
Metabolism	hepatic
Onset of action	6 hours
Biological half-life	27–58 hours
Excretion	biliar (30%) and urine (57%) as glucuronides, 3–4% as unchanged drug
Identifiers
IUPAC name N-Methyl-9,10-ethanoanthracene-9(10H)-propanamine
CAS Number	10262-69-8 Y
PubChem CID	4011
IUPHAR/BPS	2402
DrugBank	DB00934 Y
ChemSpider	23719117 N
UNII	2U1W68TROF
KEGG	D02566 Y
ChEMBL	CHEMBL21731 Y
ECHA InfoCard	100.030.532
Chemical and physical data
Formula	C20H23N
Molar mass	277.403 g/mol
3D model (Jmol)	Interactive image
SMILES CNCCC[C@@]12C3=CC=CC=C3[C@@H](C4=CC=CC=C14)CC2
InChI InChI=1S/C20H23N/c1-21-14-6-12-20-13-11-15(16-7-2-4-9-18(16)20)17-8-3-5-10-19(17)20/h2-5,7-10,15,21H,6,11-14H2,1H3/t15-,20+ N Key:QSLMDECMDJKHMQ-GSXCWMCISA-N N
NY (what is this?)  (verify)

Maprotiline (sold as Deprilept, Ludiomil, Psymion) is a medication that belongs to tetracyclic antidepressants (TeCA), a specific group of antidepressants.

History

Maprotiline was developed and has been marketed by the Swiss manufacturer Geigy (now operated by Novartis) since the early 1980s under the brand name Ludiomil. Generics are widely available.

Pharmacokinetics

After oral use absorption is good. It binds to plasma proteins 80–90%. Maximal plasma concentration is reached 6 hours after use. The mean time to peak is 12 hours. The half-life of elimination averages 51 hours.

Pharmacodynamics

Activity profile

Maprotiline exhibits strong effects as a norepinephrine reuptake inhibitor with only weak actions the reuptake of serotonin and dopamine. It is also a strong antagonist of the H₁ receptor, a moderate antagonist of the 5-HT₂ and α₁-adrenergic receptors, and a weak antagonist of the D₂ and maCh receptors.

Maprotiline has also more recently been identified as a potent antagonist of the 5-HT₇ receptor, with this action potentially playing an important role in its antidepressant effectiveness.

Discussion

The pharmacological profile of maprotiline explains its antidepressant, sedative, anxiolytic, and sympathomimetic activities. In accordance to the pharmacological characteristics it is used in the treatment of depression, such as depression associated with agitation or anxiety. Additionally, it shows strong antagonism against reserpine-induced effects in animal studies, as do the other 'classical' antidepressants. Although maprotiline behaves in most regards as a 'first-generation antidepressant' it is commonly referred to as 'second-generation antidepressant'.

The postulated mechanism of maprotiline is that it acts primarily by potentiation of central adrenergic synapses by blocking reuptake of norepinephrine at nerve endings. This pharmacological action is thought to be primarily responsible for the drug's antidepressant and anxiolytic effects. It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake. At higher doses however, maprotiline increases serotonergic transmission and increases the level of serotonin available.

Indications

Maprotiline is used in the treatment of depression, such as depression associated with agitation or anxiety and has similar efficacy to the antidepressant drug moclobemide.

• Treatment of depressions of all forms and severities (endogenous, psychotic, involutional, and neurotic) especially for depression associated with agitation or anxiety
• Panic disorder
• Neuropathic pain
• Treatment of the depressive phase in bipolar depression
• For the symptomatic relief of anxiety, tension or insomnia

The use of maprotiline in the treatment of enuresis in pediatric patients has so far not been systematically explored and its use is not recommended.

Side effects

The side-effect profile is comparable to other tri-/tetracyclic antidepressants and many of the following are due to anticholinergic (which are less prominent than those of most tricyclic antidepressants) and antihistaminergic effects. Most often seen are:

• Dizziness
• Drowsiness
• Somnolence
• fatigue
• Dry mouth (and complications of long-term uncontrolled dry mouth such as dental caries)
• Constipation
• Vertigo
• Nausea (rare, incidence of ~2%) and vomiting
• Increased appetite and weight gain
• Orthostatic hypotension, hypertension, sinus tachycardia, heart-block, arrhythmias and other cardiac effects
• Sexual dysfunction in men: impotence, priapism, delayed ejaculation, anejaculation, decreased libido
• Sexual dysfunction in women: decreased libido, vaginal dryness, painful sexual intercourse, anorgasmia
• Allergic skin reactions such as rash or urticaria (more often than with other antidepressants). Rarely, severe skin reactions such as erythema multiforme can occur.
• Photosensitivity
• Agitation, confusion
• Induction of hypomania or mania in patients suffering from underlying bipolar affective disorder
• Psychotic symptoms
• Tremor
• Extrapyramidal symptoms
• Headache
• Seizures (at high doses)
• Rare haematological complications: leukopenia and agranulocytosis (dangerous fall in white blood cells)
• Fever
• Urinary retention

Maprotiline causes a strong initial sedation (first 2 to 3 weeks of therapy) and is therefore indicated to treat agitated patients or those with suicidal risks. It causes anticholinergic side effects (dry mouth, constipation, confusion, tachycardia) with a lower incidence than amitriptyline. Originally, the manufacturer claimed that maprotiline is better tolerated than other tri-/tetracyclic drugs. However, seizures, leukopenia and skin reactions occur more often with maprotiline than with comparable drugs like amitriptyline.

Drug abuse and dependence

Maprotiline has no known potential for abuse and psychological dependence.

Withdrawal symptoms frequently seen when treatment with maprotiline is stopped abruptly (agitation, anxiety, insomnia, sometimes activation of mania or rebound depression) are not indicative of addiction and can be avoided by reducing the daily dose of maprotiline gradually by approximately 25% each week. If treatment has to be stopped at once due to medical reasons, the use of a benzodiazepine (e.g. lorazepam, clonazepam, or alprazolam) for a maximum of 4 weeks as needed will usually suppress withdrawal symptoms.

Contraindications

Maprotiline may worsen psychotic conditions like schizophrenia and should be given with caution. The antipsychotic treatment should be continued. Patients with bipolar affective disorder should not receive antidepressants whilst in a manic phase, as antidepressants can worsen mania.

Absolute

• Hypersensitivity to maprotiline or to other tri-/tetracyclic antidepressants
• Hypertrophy of the prostate gland with urine hesitancy
• Closed angle glaucoma

Special caution needed

• Concomitant treatment with a MAO-inhibitor
• Serious impairment of liver and kidney function
• Epilepsy and other conditions that lower the seizure threshold (active brain tumors, alcohol withdrawal, other medications)
• Serious cardiovascular conditions (arrhythmias, heart insufficience, state after myocardial infarction etc.)
• Treatment of patients under age 18

Suicidal patients

Same as other antidepressants, maprotiline increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of maprotiline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Maprotiline is not approved for use in pediatric patients.

Special populations

Pregnancy

Reproduction studies have been performed in female laboratory rabbits, mice, and rats at doses up to 1.3, 7, and 9 times the maximum daily human dose respectively and have revealed no evidence of impaired fertility or harm to the fetus due to maprotiline. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing mothers

Maprotiline is excreted in breast milk. At steady-state, the concentrations in milk correspond closely to the concentrations in whole blood. Caution should be exercised when maprotiline hydrochloride is administered to a nursing woman.

Pediatric use

Safety and effectiveness in the pediatric population have not been established. Anyone considering the use of Maprotiline in a child or adolescent must balance the potential risks with the clinical need.

Elderly patients

In general, lower dosages are recommended for patients over 60 years of age. Dosages of 50 mg to 75 mg daily are usually satisfactory as maintenance therapy for elderly patients who do not tolerate higher amounts.

Interactions

Maprotiline has a wide range of possible interactions. Some are typical for tri-/tetracyclic antidepressants, others are caused by specific metabolic effects (e.g. high plasma-protein-binding) of maprotiline:

• Irreversible MAO-inhibitors: agitation, delirium, coma, hyperpyrexia (high fever), seizures and severe changes in blood pressure. Treatment-resistant and hospitalized patients may be treated concomitantly with an MAO-inhibitor, if they are closely monitored and if the initial dose of the MAO-Inhibitor is low.

Increased drug actions:

• Other antidepressants, barbiturates, narcotics, sedating antihistaminics, anticonvulsive drugs, alcohol - resulting in increased central depression
• Anticholinergics (antiparkinsonian agents, tri- and tetracyclic antidepressants) - resulting in increased anticholinergic action (dry mouth, constipation etc.)
• Sympathomimetics (also those used in local anesthetics like noradrenaline) : sympathomimetic effects increased (increased blood pressure, pulse rate, paleness of skin etc.)
• Nitrates and antihypertensives (e.g. beta-blockers) - increased antihypertensive action with pronounced fall in blood pressure

Decreased drug actions:

• Guanethidine, Reserpine, Guanfacine : antihypertensive effects decreased
• Clonidine : antihypertensive effects decreased and risk of (massive) rebound hypertension.

Other types of interaction:

• Drugs, which induce certain enzymes in the liver, e.g. barbiturates, phenytoin, carbamazepine and oral anticonceptive drugs, enhance the elimination of maprotiline and decrease its antidepressant effects. Additionally the blood-concentrations of phenytoin or carbamazepine may be increased, leading to a higher incidents of side effects.
• The concomitant use of maprotiline and neuroleptics can lead to increased maprotiline blood-levels and to seizures. Combining maprotiline and thioridazine could induce severe arrhythmias.
• Additionally, increased blood-levels of Maprotiline are possible, if certain beta-blocking agents (e.g. Propranolol) are given concomitantly.
• Maprotiline may amplify the actions of coumarin-type anticogulants (e.g. warfarin, phenprocoumon). The plasma-prothrombin-activity must be assessed closely in order to avoid overt bleedings.
• Maprotiline can increase the actions of oral antidiabetic drugs (sulfonylureas) and Insulin. Diabetic patients should have regular assessments of their blood-glucose-levels.
• The concomitant application with fluoxetine or fluvoxamine may lead to significantly increased plasma-levels of maprotiline with a high incidence of maprotiline side effects. Due to the long half-lives of fluoxetine and fluvoxamine this effect may persist.

Dose forms

• Coated Tablets, 10 mg, 25 mg, 50 mg, and 75 mg
• Injectable concentrate, 25 mg

Brand names

• Ludiomil, Deprilept, Psymion
• Generics

See also

• Benzoctamine

Notes

References

• B. Bandelow, S. Bleich, S. Kropp : Handbuch Psychopharmaka (German), 2nd. edition, 2004
• Benkert, Hippius : Kompendium der Psychiatrischen Pharmakotherapie (German), 4th. edition, 2003

External links

• Maprotiline drug information
• rxlist.com
• Schweizer Arzneikompendium (German)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 三環系抗うつ剤および四環系抗うつ剤：薬理学、投与、および副作用 tricyclic and tetracyclic drugs pharmacology administration and side effects
• 2. 緩和ケアにおけるうつ病の評価およびマネージメント assessment and management of depression in palliative care
• 3. 三環系抗うつ剤中毒 tricyclic antidepressant poisoning
• 4. 非定型抗うつ薬：薬理学、投与方法、および副作用 atypical antidepressants pharmacology administration and side effects
• 5. 慢性非癌性疼痛治療の概要 overview of the treatment of chronic non cancer pain

English Journal

• Prescription patterns of Chinese herbal products for patients with sleep disorder and major depressive disorder in Taiwan.

• Chen YL1, Lee CY2, Huang KH3, Kuan YH2, Chen M4.
• Journal of ethnopharmacology.J Ethnopharmacol.2015 Aug 2;171:307-16. doi: 10.1016/j.jep.2015.05.045. Epub 2015 Jun 9.
• ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal products (CHPs) are commonly prescribed for sleep disorder and major depressive disorder (MDD). The aim of this study was to investigate the prescription patterns of CHPs and Western medicine for patients with these disorders in Taiwan, and analyze the
• PMID 26068429

• Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials.

• Hayasaka Y1, Purgato M2, Magni LR3, Ogawa Y1, Takeshima N1, Cipriani A4, Barbui C2, Leucht S5, Furukawa TA1.
• Journal of affective disorders.J Affect Disord.2015 Jul 15;180:179-84. doi: 10.1016/j.jad.2015.03.021. Epub 2015 Mar 31.
• BACKGROUND: Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the pres
• PMID 25911132

• Screen of FDA-approved drug library identifies maprotiline, an antibiofilm and antivirulence compound with QseC sensor-kinase dependent activity in Francisella novicida.

• Dean SN1, van Hoek ML.
• Virulence.Virulence.2015 Jul 4;6(5):487-503. doi: 10.1080/21505594.2015.1046029.
• Development of new therapeutics against Select Agents such as Francisella is critical preparation in the event of bioterrorism. Testing FDA-approved drugs for this purpose may yield new activities unrelated to their intended purpose and may hasten the discovery of new therapeutics. A library of 420
• PMID 26155740

Japanese Journal

• Clinical trial of Ludiomil^R in various subtypes of geriatric depression

• ASAKURA M
• Shinyaku to Rinsho 36, 1027-1036, 1987
• NAID 80003437522

• 1日1回投与法によるLudiomilの薬効評価

• 木村 政資 [他]
• 臨牀と研究 60(3), p987-994, 1983-03
• NAID 40003788267

• 産婦人科領域におけるデプレッションに対する新しい抗うつ剤LUDIOMILの臨床効果

• 長谷川 直義
• 産婦人科の世界 34(3), p307-315, 1982-03
• NAID 40001498480

Related Links

• ルジオミール/塩酸マプロチリン

抗ウツ薬 一般名 塩酸マプロチリン 商品名： 「クロンモリン」「ノイオミール」「マプレス」「マプロミール」「ルジオミール」 作 用 機 序 直接脳に働いて、精神活動を活発にし、意欲や行動性を高め、抑うつ状態を改善します。

• Ludiomil - FDA prescribing information, side effects and uses

C96-65 (Rev. 11/96) 666536 Ludiomil ® maprotiline hydrochloride tablets USP Prescribing Information Ludiomil Description Ludiomil, maprotiline hydrochloride USP, is a tetracyclic antidepressant, available as 25-mg, 50-mg and 75 ...

Related Pictures

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★リンクテーブル★

リンク元	「マプロチリン」「maprotiline hydrochloride」

「マプロチリン」

　　[★]

英

maprotiline

同

塩酸マプロチリン maprotiline hydrochloride

商

ルジオミール Ludiomil、クロンモリン、ノイオミール、マプロミール

関

薬理学

• 向精神薬

• 抗うつ薬

• 四環系抗うつ薬

• 最初の四環系抗うつ薬。

「maprotiline hydrochloride」

　　[★]

• 塩酸マプロチリン

関

Ludiomil、maprotiline