Serotonin norepinephrine reuptake inhibitors

Serotonin-noradrenaline reuptake inhibitors ( SSNRI = Selective Serotonin-Noradrenaline Reuptake Inhibitor ; German also Selective Serotonin-Noradrenaline Reuptake Inhibitor ) are drugs that are mainly used as antidepressants . The SSNRIs (often just referred to as SNRIs ) develop their effect on the serotonin and noradrenaline transporters . The first representative of this group was the active ingredient venlafaxine in 1993 .

pharmacology

The SSNRI bind in the central nervous system to transporters of the serotonin and noradrenaline type and thereby inhibit the re-uptake of these two neurotransmitters in the presynaptic nerve cell. This increases the concentration of these two substances in the synaptic gap at the postsynaptic receptors. The result is a corresponding signal amplification and thus an amplification of an inhibition descending (descending) from the central nervous system. The antidepressant effect is - as with all antidepressants - due to the higher availability of neurotransmitters through adaptation of the receptors and similar structures, which occurs with a time latency . The dopamine system is essentially not directly affected. SSNRIs have fewer side effects than the older tricyclic antidepressants . The latter also have an antihistamine effect or modify cholinergic transmission.

Active ingredients

Venlafaxine

Milnacipran

The following serotonin norepinephrine reuptake inhibitors are approved in Germany:

Venlafaxine (trade name Trevilor )
Milnacipran ( MILNAneuraX )
Duloxetine ( Yentreve , Cymbalta )

In Austria:

Venlafaxine ( Efectin )
Milnacipran ( Ixel )
Duloxetine ( Cymbalta )

In Switzerland:

Venlafaxine (Efexor)
Duloxetine (Cymbalta)

The main difference between the three active ingredients is how much they increase the noradrenaline level: while duloxetine shows a 10-fold greater selectivity for serotonin, milnacipran blocks the reuptake of serotonin and noradrenaline to the same extent. Venlafaxine has a 30-fold greater selectivity for serotonin.

Side effects

Gastrointestinal complaints (including nausea and vomiting) occur frequently, especially at the beginning of SSNRI intake. Increased restlessness and anxiety are also often reported. The risk of gastrointestinal bleeding increases up to 2.9 times if no gastric protection agent is used.

Increased blood pressure , heart problems , excitement, sleep disorders and decreased appetite as signs of central and peripheral activation are also possible. Disorders of sexual function ( orgasm disorders , potency problems ) occur. The urination disorders observed with SSNRIs and some SSRIs became the main indication for the duloxetine preparation Yentreve .

Withdrawal syndrome

→ Main article: SSRI withdrawal syndrome

With abrupt discontinuation of SSNRIs, withdrawal symptoms can occur ( SSRI discontinuation syndrome ). The symptoms that occur are perceived as stronger compared to those when discontinuing SSRIs. Slow tapering is therefore advisable.

Children and young people

With some preparations, the risk of aggressive or autoaggressive behavior, as well as suicidal tendencies in children and adolescents, is increased. According to the recommendation of the Federal Institute for Drugs and Medical Devices, drugs of this type should, if possible, not be used unless they have been explicitly approved for this age group.

Interactions

The combination of SSNRIs with MAO inhibitors or with serotonin precursors (see prodrug ) such as tryptophan or 5-hydroxytryptophan leads to an increased risk of serotonin syndrome .

Web links

Commons : Serotonin-Norepinephrine Reuptake Inhibitors - Collection of pictures, videos and audio files

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↑ Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug . In: Neuropharmacology . 24, No. 12, 1985, pp. 1211-9. doi : 10.1016 / 0028-3908 (85) 90157-1 . PMID 3005901 .
↑ Herbert Kellner: Antidepressants can also attack the stomach . In: MMW advances in medicine . tape 151 , no. 51-52 , December 2009, pp. 49-49 , doi : 10.1007 / BF03365851 .
↑ Antidepressants: Scientific reassessment of SSRI / SNRI completed - New warnings on suicidal behavior in children and adolescents. BfArM , July 12, 2005, accessed April 29, 2017 .

[Moret-1] Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug . In: Neuropharmacology . 24, No. 12, 1985, pp. 1211-9. doi : 10.1016 / 0028-3908 (85) 90157-1 . PMID 3005901 .

[2] Herbert Kellner: Antidepressants can also attack the stomach . In: MMW advances in medicine . tape 151 , no. 51-52 , December 2009, pp. 49-49 , doi : 10.1007 / BF03365851 .

[3] Antidepressants: Scientific reassessment of SSRI / SNRI completed - New warnings on suicidal behavior in children and adolescents. BfArM , July 12, 2005, accessed April 29, 2017 .