Serotonin and noradrenalin reuptake

Selective serotonin and noradrenaline reuptake inhibitors (SNRIs)... 

Venlafaxine is a serotonin and noradrenaline reuptake inhibitor (SNRI). It shares these properties with the TCAs amitriptyhne, clomipramine and imip-ramine, but it is the first selective SNRI, with low affinity for muscarinic, histaminic and a-adrenergic receptors. At low doses serotonergic effects predominate, but at higher doses the reuptake of noradrenaline is significantly blocked (Melichar et al. 2001). It is available as immediate and extended release (XR) preparations. 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

Table 1 Clinical properties of serotonin and noradrenaline reuptake inhibitors (only those drugs are included for which a resonable number of reports on controlled clinical trials are available). For more detailed information see Onghena and van Houdenhove (1992), Philipp and Fickinger (1993), McQuay et al. (1996), and Ansari (2000).

Milnacipran (Pierre Fabre), an equipotent serotonin and noradrenaline reuptake inhibitor, was launched in 1997 as an antidepressant and was licensed for development for the treatment of fibromyalgia and related chronic pain disorders in 2001. It is currently in late preclinical development. 

VAN-H36 (Vita-Invest) is a serotonin and noradrenaline reuptake inhibitor and p-receptor agonist (i.e. has a pharmacological profile of action similar to tramadol). It is in early clinical development as an analgesic. 

Thus, although major breakthroughs in the development of serotonin and noradrenaline reuptake inhibitors as analgesics are unlikely, a refinement of treatment and cotreatment methods may still hold substantial potential in yielding improved therapeutic effectiveness of this drug class. 

The suggested mechanism of this interaction was that finasteride inhibited the hepatic metabolism of sibutramine, which then displaced finasteride from its plasma protein binding sites inhibition of 5HT (serotonin) and noradrenaline reuptake by sibutramine then triggering the psychotic event. 

Blier, P. 2006. Dual serotonin and noradrenaline reuptake inhibitors Focus on their differences. Int. J. Psych. Cl. Pr., 10(2), 22-32. 

Milnacipran Tetracyclic Inhibitor of serotonin and noradrenaline reuptake... 

A 48-year-old woman developed anxiety, tremor, depression, dry mouth, nausea, and marked weight loss (503). Physical examination, electrocardiography, chest X-ray, CT scan, and laboratory investigations were unremarkable. The Hamilton D score was 44 for 17 items. She had taken mefloquine 250 mg/week for 8 weeks for malaria prophylaxis, and after 2 weeks had started to feel unwell, with dysphoria, depression, and weakness. She was given fluoxetine 20 mg/day and alprazolam 1.5 mg/day. Her condition continued to deteriorate. The dose of fluoxetine was increased to 40 mg/day and flunitrazepam was added. She was later instead given milnacipran, a serotonin and noradrenaline reuptake... 

Within each class or subclass drugs are listed in order of frequency of prescription in the United Kingdom (1997 data). Abbreviations RIMA—reversible inhibitor of monoamine oxidase NaRI—noradrenaline reuptake inhibitor SNRI—serotonin and noradrenaline reuptake inhibitor NaSSA—noradrenaline and specific serotonergic antidepressant. 

Antidepressants in this group include duloxetine, milnacipran and venla-faxine. They inhibit both serotonin and noradrenaline reuptake but with differing selectivity. Milnacipran blocks serotonin and noradrenaline reuptake approximately equally, but duloxetine and to a greater extent ven-lafaxine have selectivity for serotonin. Duloxetine and venlafaxine are reported to weakly inhibit dopamine reuptake. They are also reported to have no significant affinity for histaminergic, muscarinic or adrenergic receptors, and, compared with the tricyclics, appear to lack significant sedative and antimuscarinic effects. 

Indirect effects of drugs on catecholamines have ako resulted in takotsubo syndrome. In one case there was transient typical ballooning of the left ventricular apex during systole following the use of cocaine, thought to have been due to inhibition of catecholamine reuptake [22ft]. A 43-year-old woman who took an overdose of venlafaxine, an inhibitor of serotonin and noradrenaline reuptake, developed a takotsubo cardiomyopathy and there was an increase in urinary normetadrenaline (normetanephrine) concentration [23 ]. 

Falls SSRIs and serotonin and noradrenalin reuptake inhibitors (SNRIs) have long been linked with an increased risk of osteopenia/osteoporosis potentiating falls and fractures, especially in tiie elderly. A biological mechanism for these risks associated with SSRIs has been idenhfied. Studies have demonstrated a reduction in osteoblast proliferation and activity following treatment with SSRIs, the magnitude of such effects being linked to affinity to the serotonin transporter. In addition, recent research examining serotonin receptor expression in human osteoblasts and osteoclasts has found that SSRIs differentially inhibit bone cells via apoptosis [10 ]. 

Hallback I, Hagg S, Eriksson AC, Whiss PA. In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation. Pharmacol Rep 2012 64(4) 979-83. 

Reverse transcriptase polymerase chain reaction Short-acting beta-adrenoceptor agonist Standardized mortality rate Single nucleotide polymorphism Serotonin and noradrenaline reuptake inhibitor Selective serotonin reuptake inhibitor Simian virus 40... 

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