Serotonin-noradrenaline reuptake inhibitors (SNRIs) are medications that increase the levels of serotonin and noradrenaline in the body, especially in the brain, hence producing a number of characteristic effects, both therapeutic and adverse.
Many TCAs are SNRIs too, although the term SNRI is usually reserved for agents with minimal affinity towards the mAChRs, H1 and adrenergic receptors.
The major therapeutic actions of them include pain relief (especially against neuropathic pain), antidepressant effects, anxiolytic (anti-anxiety) effects and may relieve urinary incontinence.
|Other indications; notes|
|Desvenlafaxine||Major depressive disorder.||Major depression.||Depression.||None yet.|
|Duloxetine||Major depressive disorder, painful diabetic peripheral neuropathy, chronic musculoskeletal pain, fibromyalgia and generalized anxiety disorder.||Major depressive disorder, generalized anxiety disorder and painful diabetic peripheral neuropathy.||Major depressive disorder, generalized anxiety disorder, stress urinary incontinence and diabetic neuropathy.||None notable.|
|Levomilnacipran||Major depressive disorder.||Not approved.||Not approved.||None notable.|
|Milnacipran||Fibromyalgia.||Fibromyalgia.||Not approved.||None notable.|
|Venlafaxine||Depression, generalised anxiety disorder, panic disorder and social phobia.||Major depression, generalised anxiety disorder, panic disorder and social phobia.||Depression, generalised anxiety disorder, panic disorder and social phobia.||Neuropathic pain.|
Their principal side effects include: digestive complaints (like dry mouth, nausea/vomiting, diarrhoea and constipation), sexual dysfunction, headache, dizziness, urinary problems,[note 1] agitation, anxiety, insomnia, drowsiness, weight loss or gain, etc. SNRIs include: desvenlafaxine, duloxetine, levomilnacipran, milnacipran and venlafaxine.
Mechanism of actionEdit
Their half-lives are all less than or equal to 12 hours, hence twice or three times daily dosing is required, except where extended release formulations are available (like for venlafaxine and desvenlafaxine). They generally have pretty minimal effects on P450 enzymes, aside from duloxetine which is a moderate inhibitor of CYP2D6.
|Plasma protein binding||Half-life||Metabolizing enzymes||Enzyme effects.||Dosing frequency|
|Desvenlafaxine||80%||30%||11 hours||UDP-mediated conjugation and CYP3A4-mediated metabolism (minor).||CYP2D6 inhibition (weak).||qDay (XR).|
|Duloxetine||?||>90%||11-12 hours||CYP2D6 and CYP1A2-mediated metabolism||CYP2D6 inhibition (moderate).||q12hr.|
|Levomilnacipran||92%||22%||12 hours||CYP3A4 with minor contribution by CYP2C8, 2C19, 2D6, and 2J2.||None.||qDay.|
|Milnacipran||85-90%||13%||6-8 hours (L-isomer), 8-10 hours (D-isomer)||CYP3A4.||None.||q12hr.|
|Venlafaxine||45%||27-30%||5 hours||CYP2D6-mediated O-demethylation to desvenlafaxine. CYP3A4-mediated metabolism also contributes.||CYP2D6 inhibited (weak)||q8-12hr.|
- NCBI Bookshelf provides free book resources on this topic.
- PubMed provides review articles from the past five years (limit to free review articles or to systematic reviews)
- The TRIP database provides clinical publications about evidence-based medicine.
- ↑ Including reduced urination, difficulty passing urine and sometimes people will quit urinating altogether
- ↑ Also derived from the PDSP database
- ↑ Other sources include AMH, Martindale, Medscape Reference and review articles
- ↑ Bioavailability
- ↑ 1.0 1.1 Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York, USA: McGraw-Hill Professional. ISBN 978-0-07-162442-8.