They are specific 5-HT and various degrees NE reuptake inhibition. Venlafaxine, at lower doses (75–100 mg/day) acts as SSRI. As the dose increases it inhibit NE reuptake (& 2ry ↓ DA reuptake in prefrontal cortex, which lacks DAT→ ↑ DA).

1. Serotonin Norepinephrine
Reuptake Inhibitors (SNRIs)
Prof. Sawsan Aboul-Fotouh
Department of pharmacology, faculty of Medicine, Ain-Shams University
SNRIs

2. Serotonin Norepinephrine Reuptake
Inhibitors (SNRIs)
Venlafaxine Duloxetine
Desvenlafaxine Levomilnacipran
Milnacipran

3. They are specific 5-HT and various
degrees NE reuptake inhibition.
Venlafaxine, at lower doses (75–100 mg/day) acts as
SSRI. As the dose increases it inhibit NE reuptake
(& 2ry ↓ DA reuptake in prefrontal cortex, which
lacks DAT→ ↑ DA).
Mechanism of action of SNRIs

4. Advantage & side effects of SNRIs
No Autonomic Blockade
H1 M 
Adverse Effects
-Nausea, headache, sexual dysfunction, insomnia.
-Hypertension & ↑HR (in high dose). “NE”

5. Desvenlafaxine inhibits reuptake of NE > 5-HT
(Stahl ҆s essential psychopharmacology, 2013)
Desvenlafaxine is not affected by CYP2D6 inducers & inhibitors
Desvenlafaxine has similar efficacy, indications, Pharmacodynamic
& Side effects as venlafaxine
• Venlafaxine has half-life of ̴ 6 h and Desvenlafaxine has half-life of ̴ 12 h.

6. Duloxetine indicated in stress
urinary incontinence

7. ▪ Liver disease 
▪ Severe renal impairment, end stage renal
disease (dialysis) (CrCl<30)
▪Moderate to heavy alcohol use.
Contraindications of Duloxetine

8. Milnacipran
(Stahl ҆s essential psychopharmacology, 2013)
Therapeutic indications
A. FDA-approved
1. Fibromyalgia (Milnacipran only, 2009)
2. Major depressive disorder (Levomilnacipran only, 2013)
B. Non FDA-approved
1. Neuropathic pain/Chronic pain (Both)
Milnacipran and Levomilnacipran
The 5-HT: NE ratios of SNRIs are: Venlafaxine = 30:1, Desvenlafaxine = 10:1, Duloxetine = 10:1,
Milnacipran = 1:1, and Levomilnacipran = 1:2 (Randy and Lori, 2014)
Adverse Effects as SNRIs but More insomnia, & ↓appetite (as > ↑NE)

9. 1. Depressive disorders
2. Anxiety disorders (GAD, …….)
3. Post-traumatic stress disorder.
4. Neuropathic pain, Diabetic NP (Duloxetine , FDA 2004).
5. Fibromyalgia: (Duloxetine , 2008 & Milnacipran, 2009 ) and
Chronic musculoskeletal pain, (Duloxetine , FDA 2010).
6. Stress Incontinence (Duloxetine , off-label)
7. Vasomotor menopausal symptoms….
Q: Therapeutic Uses of SNRIs