Trimipramine

• (RS ) -3 - ( 10,11- dihydro -5H- dibenzo [ b, f] azepin- 5-yl) -N, N ,2- trimethylpropane - 1-amine (IUPAC)
• (±) -3 - ( 10,11- dihydro -5H- dibenzo [ b, f] azepin- 5-yl) -N, N ,2- trimethylpropane - 1-amine
• Rac -3-( 10,11- dihydro -5H- dibenzo [ b, f] azepin- 5-yl) -N, N ,2- trimethylpropane - 1-amine
• DL -3-( 10,11- dihydro -5H- dibenzo [ b, f] azepin- 5-yl) -N, N ,2- trimethylpropane - 1-amine

• 739-71-9
• 521-78-8 ( maleate )
• 25332-13-2 ( monomesylate )

N06AA06

Tricyclic antidepressant, anxiolytic

Blocks serotonin, dopamine and α -adrenoceptors

45 ° C.

Maleate

Attention

• 250 mg · kg -1 ( LD50, mouse, oral)
• 42 mg · kg -1 ( LD50, mouse, i.v.)
• 425 mg · kg -1 ( LD50, Mouse, oral, maleate )
• 40 mg · kg -1 ( LD50, mouse, i.v. maleate )
• 800 mg · kg -1 ( LD50, Rat, oral, maleate )
• 38 mg · kg -1 ( LD50, rat, i.v. maleate )

Template: Infobox chemical / molecular formula search available

Trimipramine is a dibenzazepine, which is used as a drug from the group of tricyclic antidepressants. Its effect is especially strong damping, and anxiolytic.

Effect

Trimipramine blocked various serotonin, dopamine, and α -adrenoceptors in the central nervous system. Monoamine reuptake from the synaptic cleft into presynaptic vesicles is not affected. Thus, the antidepressant mechanism of action is different from that of other tricyclic antidepressants. In addition, anticholinergic and antihistaminic effect of trimipramine; but it has, therefore, consequently, the characteristic monitoring and side effects of other tricyclic antidepressants. Trimipramine also acts as FIASMA ( functional inhibitors of acid sphingomyelinase ).

Due to the comparatively lower influence of serotonin and norepinephrine, the antidepressant effects are less pronounced. Therefore, it finds its use especially in anxious - agitated depression with restlessness, anxiety, sleep-wake rhythm disorders, but also for the treatment of monosymptomatic sleep. The sedative effect can be very strong; For this reason, the daily dose is taken up mainly in the evening. Daytime sleepiness but occurs almost always, especially at start.

The half-life in the human body trimipramine is 24 hours.

Indications

Trimipramine is approved for the treatment of depression, especially if anxiety and insomnia are as symptoms in the foreground.

It can also be used in low doses for the adjuvant treatment of chronic pain.

The application as a hypnotic is popular. However, since no useful evidence of efficacy even after years of off- label use and the alleged compatibility advantages over doxepin could be, inter alia, never occupied, still exists not approved as a sleep- promoting agent.

Contraindications

Trimipramine should not be used:

• In acute alcohol, hypnotics, analgesics and Psychopharmakaintoxikation,
• In acute delirium,
• With untreated angle closure glaucoma,
• At Harnentleerungsstörungen as urinary retention or prostatic hyperplasia with residual urine,
• With pyloric stenosis,
• With paralytic ileus,
• With concurrent use of irreversible MAO inhibitors,
• In pregnancy and lactation.

Adverse effects

Trimipramine may especially autonomic side effects (dry mouth, hypotension, tachycardia, mydriasis and accommodation disorders, gastrointestinal problems, voiding dysfunction, etc) have.

Moreover, inter alia, Changes in blood count ( leukopenia, agranulocytosis ) may occur, further weight gain (mainly by water retention) as well as mood swings.

Absetzproblematik

After prolonged treatment can Abrupt discontinuation nausea, headache and malaise lead. In addition, sleep disorders, anxiety, restlessness, and increased irritability can occur. The treatment should be stopped gradually.

Dosage forms

Trimipramine is offered in the form of tablets, dragees, or as a solution.

Use in pregnancy

May trimipramine during pregnancy and lactation can not be applied due to lack of experience for doing so, and limited studies in animals have shown evidence of harm to the offspring (increased mortality and malformations).

Genotoxic potential

In experiments on the Drosophila trimipramine led to DNA damage. According to a study taking trimipramine may increase breast cancer risk.

Production and stereochemistry

The synthesis is carried out starting from 10,11, dihydro -5H- dibenz [b, f] azepine by deprotonation with sodium amide and a nucleophilic substitution with racemic 3-N, N- dimethylamino-2- methylpropylchlorid. Trimipramine contains a stereogenic center, of the drug is, however, used as a racemate.

Trade names

Herphonal (D), Stangyl (D), Surmontil (CH ), numerous generics (D, CH)