関: trimipramine、trimipramine maleate

WordNet

tricyclic antidepressant drug (trade name Surmontil) used to treat depression and anxiety and (sometimes) insomnia (同)Surmontil

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/02 00:56:49」(JST)

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Trimipramine (Surmontil, Rhotrimine, Stangyl) is a tricyclic antidepressant (TCA) with antipsychotic and sedative properties.

Medical uses

Trimipramine's primary use in medicine is in the treatment of major depressive disorder,^[5]^[6] especially where sedation is required due to its prominent sedative effects.^[6] Trimipramine also has some weak antipsychotic effects which are less pronounced than with the phenothiazine antipsychotic perazine.^[7]^[8]^[9]

Trimipramine is the only effective drug against insomnia known so far that does not alter the normal sleep architecture (there is evidence in medical journals that refute this last statement^{[weasel words]}^{[citation needed]}). In particular, it does not suppress REM sleep, and dreams are said to brighten during treatment.^[10]

Adverse effects

Common adverse effects include:^[1]^[2]^[3]^[4]^[5]^[6]

Note: Bolded adverse effects are serious ones.

Sedation — especially common with trimipramine compared to the other TCAs
Anticholinergic effects including:

- dry mouth

- blurred vision

- mydriasis

- decreased lacrimation

- constipation

- urinary hesitancy or retention

- reduced GI motility

- tachycardia (high heart rate)

- anticholinergic delirium (particularly in the elderly and in Parkinson's disease)

Weight gain
Orthostatic hypotension
Sexual dysfunction including impotence, loss of libido and other sexual adverse effects
Tremor
Dizziness
Sweating
Anxiety
Insomnia
Agitation
Rash

whereas adverse effects with an unknown incidence includes:^[1]^[2]^[3]^[4]^[5]^[6]

Confusion
Nausea
Vomiting
Extrapyramidal side effects (e.g. parkinsonism, dystonia, etc.)
Tinnitus
Paraesthesia
ECG changes
Increased liver function tests

and rare adverse effects include:^[1]^[2]^[3]^[4]^[5]^[6]

Seizures
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
Blood dyscrasias including:

- Agranulocytosis

- Thrombocytopenia

- Eosinophilia

- Leukopaenia

Myocardial infarction
Heart block
QTc interval prolongation
Sudden cardiac death
Depression worsening
Suicidal ideation

Contraindications

Contraindications include:^[1]^[2]^[3]^[4]^[5]^[6]

Recent myocardial infarction
Any degree of heart block or other cardiac arrhythmias
Mania
Severe liver disease
During breast feeding
Hypersensitivity to trimipramine maleate or to any of the excipients

Interactions

Trimipramine should not be given with sympathomimetic agents such as adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine and phenylpropanolamine.

Barbiturates may increase the rate of metabolism. Trimipramine should be administered with care in patients receiving therapy for hyperthyrodism.^[1]^[2]^[3]^[4]^[5]^[6]

Overdose

Compared to other tricyclic antidepressants trimipramine is relatively safe in overdose, although it is more dangerous than the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) but less dangerous than bupropion in cases of overdose.^[11]

Mechanism of action

Trimipramine's mechanism of action differs from other TCAs. It is a weak to moderate^[12] reuptake inhibitor of serotonin, and an extremely weak inhibitor of norepinephrine and dopamine reuptake. Its main effects are due to considerable receptor antagonism as follows:^[9]^[12]^[13]

Very strong: H₁
Strong: 5-HT_2A, α₁-adrenergic
Moderate: D₂, mACh
Weak: 5-HT_2C, D₁, α₂-adrenergic

Transporter/Receptor	K_i (nM)^[9]^[12]^[13]	Species
SERT	149	Human
NET	2450	Human
DAT	3780	Human
H₁	1.4	Human
α₁	24	Rat
α_2A	1380	Rat
α_2B	380	Rat
mAChRs	59	Human
5-HT_2A	19.5	Rat
5-HT_2C	537	Rat
5-HT₃	9120	Rat
D₁	347	Rat
D₂	57.5	Rat

Pharmacokinetics

Trimipramine is a racemic compound with two enantiomers.^[1] CYP2C19 is responsible for the demethylation of (D)- and (L)-trimipramine to (D)- (L)-desmethyltrimipramine, respectively, and CYP2D6 is responsible for the 2-hydroxylation of (D)- and (L)-desmethyltrimipramine to (D)- and (L)-2-hydroxydesmethyltrimipramine, respectively.^[14] CYP2D6 also metabolizes (L)-trimipramine into (L)-2-hydroxytrimipramine.^[14]

History

Trimipramine maleate (as Surmontil) oral capsules were first approved by the Food and Drug Administration prior to January 1, 1982 in 25 mg and 50 mg formulations, with the 100 mg formulation having been approved on September 15, 1982. A generic version of all three formulations was given FDA approval on August 2, 2006.^[15]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "PRODUCT INFORMATION SURMONTIL® Tablets and Capsules" (PDF). TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. 28 November 2012. Retrieved 30 November 2013.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "SURMONTIL (trimipramine maleate) capsule [Duramed Pharmaceuticals Inc]". DailyMed. Duramed Pharmaceuticals Inc. December 2012. Retrieved 30 November 2013.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Surmontil, Trimip (trimipramine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 30 November 2013.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Trimipramine 50mg Capsules - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 19 November 2012. Retrieved 30 November 2013.
^ ^a ^b ^c ^d ^e ^f Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
^ ^a ^b ^c ^d ^e ^f ^g Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
^ Bender, S; Olbrich, HM; Fischer, W; Hornstein, C; Schoene, W; Falkai, P; Haarmann, C; Berger, M; Gastpar, M (March–April 2003). "Antipsychotic efficacy of the antidepressant trimipramine: a randomized, double-blind comparison with the phenothiazine perazine". Pharmacopsychiatry 36 (2): 61–69. doi:10.1055/s-2003-39043. PMID 12734763.
^ Eikmeier, G; Berger, M; Lodemann, E; Muszynski, K; Kaumeier, S; Gastpar, M (Winter 1991). "Trimipramine: An atypical neuroleptic?". International Clinical Psychopharmacology 6 (3): 147–153. doi:10.1097/00004850-199100630-00003. PMID 1806621.
^ ^a ^b ^c Gross, G; Xin, X; Gastpar, M (November 1991). "Trimipramine: Pharmacological reevaluation and comparison with clozapine". Neuropharmacology 30 (11): 1159–1166. doi:10.1016/0028-3908(91)90160-D. PMID 1663593.
^ Schredl, M; Berger, M; Riemann, D (May 2009). "The effect of trimipramine on dream recall and dream emotions in depressive outpatients". Psychiatry Research 167 (3): 279–286. doi:10.1016/j.psychres.2008.03.002. PMID 19403177.
^ White, N; Litovitz, T; Clancy, C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type" (PDF). Journal of Medical Toxicology 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.
^ ^a ^b ^c Roth, BL; Driscol, J (12 January 2011). "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 30 November 2013.
^ ^a ^b Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
^ ^a ^b Eap CB, Bender S, Gastpar M et al. (2000). "Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients". Ther Drug Monit 22 (2): 209–14. doi:10.1097/00007691-200004000-00012. PMID 10774635.
^ "Generic Surmontil Availability". Drugs.com. Retrieved 22 March 2013.

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. 睡眠の質および睡眠の構造に対する薬剤の効果 the effects of medications on sleep quality and sleep architecture
3. 小児単極性うつ病および薬物療法：薬剤の選択 pediatric unipolar depression and pharmacotherapy choosing a medication
4. 身体化：治療および予後 somatization treatment and prognosis

English Journal

Electromembrane extraction through a virtually rotating supported liquid membrane.

HosseinyDavarani SS1, Moazami HR2, Memarian E1, Nojavan S1.
Electrophoresis.Electrophoresis.2016 Jan;37(2):339-46. doi: 10.1002/elps.201500296. Epub 2015 Nov 17.
Electromembrane extraction (EME) of model analytes was carried out using a virtually rotating supported liquid membrane (SLM). The virtual (nonmechanical) rotating of the SLM was achieved using a novel electrode assembly including a central electrode immersed inside the lumen of the SLM and five cou
PMID 26462723

Drug-Induced Liver Injury during Antidepressant Treatment: Results of AMSP, a Drug Surveillance Program.

Friedrich ME1, Akimova E1, Huf W1, Konstantinidis A1, Papageorgiou K1, Winkler D1, Toto S1, Greil W1, Grohmann R1, Kasper S1.
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP).Int J Neuropsychopharmacol.2015 Dec 30. pii: pyv126. doi: 10.1093/ijnp/pyv126. [Epub ahead of print]
BACKGROUND: Drug-induced liver injury is a common cause of liver damage and the most frequent reason for withdrawal of a drug in the United States. The symptoms of drug-induced liver damage are extremely diverse, with some patients remaining asymptomatic.METHODS: This observational study is based on
PMID 26721950

Drug-induced liver injury associated with antidepressive psychopharmacotherapy: An explorative assessment based on quantitative signal detection using different MedDRA terms.

Gahr M1, Zeiss R1, Lang D2, Connemann BJ1, Hiemke C3, Schönfeldt-Lecuona C1.
Journal of clinical pharmacology.J Clin Pharmacol.2015 Oct 16. doi: 10.1002/jcph.662. [Epub ahead of print]
Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with antidepressive psychopharmacotherapy. However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepressants. We performed a quantitative signa
PMID 26470856

Japanese Journal

うつ病に対するTrimipramine(Surmontil)の効果--Medazepam(Pesmit)との併用について

高階憲司
臨牀と研究 54(11), p3805-3814, 1977-11
NAID 40003783089

抗うつ剤,Surmontilの内科領域における使用経験

黒田正宏 [他]
臨牀と研究 51(12), p3660-3665, 1974-12
NAID 40003785041

Related Pictures

★リンクテーブル★

リンク元	「トリミプラミン」「trimipramine maleate」

「トリミプラミン」

Trimipramine
Systematic (IUPAC) name
	(±)-3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N,2-trimethylpropan-1-amine
Clinical data
Trade names	Surmontil
AHFS/Drugs.com	monograph
MedlinePlus	a602010
Licence data	US FDA:link
Pregnancy; category	AU: C; US: C (Risk not ruled out);
Legal status	AU: Prescription Only (S4); CA: ℞-only; UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Oral, IM, IV
Pharmacokinetic data
Bioavailability	41%
Protein binding	94.9%
Metabolism	Hepatic
Biological half-life	23-24 hours
Excretion	Renal
Identifiers
CAS Registry Number	739-71-9
ATC code	N06AA10
PubChem	CID: 5584
IUPHAR/BPS	7317
DrugBank	DB00726
ChemSpider	5382
UNII	6S082C9NDT
KEGG	D00394
ChEBI	CHEBI:9738
ChEMBL	CHEMBL644
Chemical data
Formula	C20H26N2
Molecular mass	294.434 g/mol
	SMILES c1cc3c(cc1)CCc2c(cccc2)N3CC(C)CN(C)C ;
	InChI InChI=1S/C20H26N2/c1-16(14-21(2)3)15-22-19-10-6-4-8-17(19)12-13-18-9-5-7-11-20(18)22/h4-11,16H,12-15H2,1-3H3 ; Key:ZSCDBOWYZJWBIY-UHFFFAOYSA-N ;
(what is this?) (verify)

　　[★]

英: trimipramine
化: マレイン酸トリミプラミン trimipramine maleate
商: スルモンチール Surmontil
関: 三環系抗うつ薬

「trimipramine maleate」

　　[★]

マレイン酸トリミプラミン

関: Surmontil、trimipramine

[TGA-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "PRODUCT INFORMATION SURMONTIL® Tablets and Capsules" (PDF). TGA eBusiness Services. Aspen Pharmacare Australia Pty Ltd. 28 November 2012. Retrieved 30 November 2013.

[DM-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "SURMONTIL (trimipramine maleate) capsule [Duramed Pharmaceuticals Inc]". DailyMed. Duramed Pharmaceuticals Inc. December 2012. Retrieved 30 November 2013.

[MSR-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Surmontil, Trimip (trimipramine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 30 November 2013.

[EMC-4] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j "Trimipramine 50mg Capsules - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 19 November 2012. Retrieved 30 November 2013.

[AMH-5] ^ ^a ^b ^c ^d ^e ^f Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.

[BNF-6] ^ ^a ^b ^c ^d ^e ^f ^g Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.

[7] Bender, S; Olbrich, HM; Fischer, W; Hornstein, C; Schoene, W; Falkai, P; Haarmann, C; Berger, M; Gastpar, M (March–April 2003). "Antipsychotic efficacy of the antidepressant trimipramine: a randomized, double-blind comparison with the phenothiazine perazine". Pharmacopsychiatry 36 (2): 61–69. doi:10.1055/s-2003-39043. PMID 12734763.

[8] Eikmeier, G; Berger, M; Lodemann, E; Muszynski, K; Kaumeier, S; Gastpar, M (Winter 1991). "Trimipramine: An atypical neuroleptic?". International Clinical Psychopharmacology 6 (3): 147–153. doi:10.1097/00004850-199100630-00003. PMID 1806621.

[Gross-9] Gross, G; Xin, X; Gastpar, M (November 1991). "Trimipramine: Pharmacological reevaluation and comparison with clozapine". Neuropharmacology 30 (11): 1159–1166. doi:10.1016/0028-3908(91)90160-D. PMID 1663593.

[10] Schredl, M; Berger, M; Riemann, D (May 2009). "The effect of trimipramine on dream recall and dream emotions in depressive outpatients". Psychiatry Research 167 (3): 279–286. doi:10.1016/j.psychres.2008.03.002. PMID 19403177.

[11] White, N; Litovitz, T; Clancy, C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type" (PDF). Journal of Medical Toxicology 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.

[PDSP-12] Roth, BL; Driscol, J (12 January 2011). "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 30 November 2013.

[GG-13] Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.

[pmid10774635-14] Eap CB, Bender S, Gastpar M et al. (2000). "Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients". Ther Drug Monit 22 (2): 209–14. doi:10.1097/00007691-200004000-00012. PMID 10774635.

[15] "Generic Surmontil Availability". Drugs.com. Retrieved 22 March 2013.

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案内

Surmontil