Serotonin and noradrenaline re-uptake inhibitors

Venlafaxine is a serotonin and noradrenaline re-uptake inhibitor indicated in depression and may be used in generalised anxiety disorder. Venlafaxine can cause diarrhoea and headache as side-effects. It does not cause blurred vision. 

Duloxetine has recently been marketed as an antidepressant in Europe. It inhibits the re-uptake of serotonin and noradrenaline, with minimal effects on other neurotransmitter mechanisms. It is therefore classified as a serotonin and noradrenaline re-uptake inhibitor (SNRI) and is grouped with venlafaxine. The adverse effect profile of duloxetine appears to be similar to that of the SSRIs and venlafaxine. In placebo-controlled trials the most common adverse effects were nausea (37%), dry mouth (32%), dizziness (22%), somnolence (20%), insomnia (20%), and diarrhea (14%). Sexual dysfunction has also been reported. Current data suggest that, unlike venlafaxine, duloxetine does not increase the blood pressure, but further post-marketing surveillance studies will be needed to confirm this (1). 

Tramake Tramal Zydol ) is a phenylcyclohexanol derivative, a (p) OPIOID RECEPTOR agonist with partial OPIOID ANALGESIC activity. It is also a monoamine (serotonin and noradrenaline) re-UPTAKE inhibitor, and this mechanism is thought independently to contribute a component to analgesic activity. 

Serotonin and Noradrenaline Re uptake Inhibitors (SNRIs) Side effects similar to SSRIs, especially GI (constipation, dry mouth, nausea), sedation/insomnia. Added risk of hypertension... 

Due to the frequent unwanted effects and, in case of tranylcypromine, the numerous and dangerous interactions MAO-inhibitors are more and more replaced by the much less problematic SSRIs. Compounds belonging to this group are citalopram, escitalopram, fluoxetine, paroxetine and sertraline. They are used clinically in the therapy of depression, bulimia and obsessive-compulsive disorders. All SSRIs show a slow onset of action (1-2 weeks). They may induce insomnia and weight loss. The antidepressant ven-lafaxine inhibits both, serotonin and noradrenaline re-uptake and might therefore additionally induce hypertension. 

Prescriptions for two substances are counted toward the totals for each substance. APAP = acetaminophen SSRI = selective serotonin reuptake inhibitor SNRI = serotonin and noradrenaline re-uptake inhibtor HCTZ = hydrochlorothiazide NSAID = non-steroid anti-inflammatory drug. Source Author s estimates based on Verispan VONA, www.drugtopics.com/drugtopics/data/articlestandard/drugtopics/092007/407652/article.pdf. ... 

The symptoms experienced by this patient were tjrpical of venlafaxine and SSRI withdrawal (although they could also be experienced after sudden withdrawal of tricyclic antidepressants). The fact that they were relieved by a serotonin but not a noradrenaline re-uptake inhibitor suggests that venlafaxine-induced withdrawal symptoms are mediated by serotonergic mechanisms. 

The selective serotonin re-uptake inhibitors (SSRIs) that are currently available are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. They are widely marketed and are in many countries a major alternative to tricyclic antidepressants in the treatment of depression. The SSRIs are structurally diverse, but they are all inhibitors of serotonin uptake, with much less effect on noradrenaline. They have slight or no inhibitory effect on histaminergic, adrenergic, serotonergic, dopaminergic, and cholinergic receptors (1). 

Citalopram is a racemic bicyclic phthalane derivative and is a highly selective serotonin re-uptake inhibitor with minimal effects on noradrenaline and dopamine neuronal reuptake. Inhibition of 5-HT re-uptake by citalopram is primarily due to escitalopram, the active S-enantiomer of citalopram (1). One would expect escitalopram to be twice as potent as citalopram but otherwise not to differ significantly from the racemic mixture. However, escitalopram is marketed as being more efficacious than citalopram because, it is argued, the inactive R-isomer present in the racemate actually inhibits binding of the S-enantiomer to its site of action, the serotonin transporter. In some, but not all, clinical trials escitalopram has been statistically superior to citalopram in terms of speed of onset of therapeutic action and improvement on depression rating scales. The clinical significance of these differences is debatable (2). 

SSRb are the most recent class, named after the drugs mechanisms of action (Selective Serotonin Reuptake Inhibitors), of which fluoxetine is the archytype. Other examples include danopramine, dtalopram, fluvoxamine, mirtazapine and paroxetine. Later members, such as venlafaxine, differ in being serotonin (re) UPTAKE INHIBITORS that also inhibit noradrenaline reuptake (but are weaker against dopamine uptake). The SSRIs show less side-effects, particularly less sedative actions, than the other classes. 

Wong DT, Bymaster FP. Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype Prog Drug Res 2002 58 169-222. 

The triazolopyridine trazodone does not have an appreciable effect on the re-uptake of the neurotrans-mittors dopamine or noradrenaline. It is a weak inhibitor of serotonin re-uptake but is a potent antagonist of the serotonin 5-HT2 receptor. Clinical experience has shown unpredictable efficacy. Trazodone has little antimuscarinic activity and has little if any action on cardiac conduction. Like mianserin it can therefore safely be used in patients for which anticholinergics are contraindicated and there are no absolute contraindications for patients with concomitant diseases of the cardiovascular system. 

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