Antidepressants serotonin-norepinephrine reuptake inhibitors

NERVOUS SYSTEM DRUGS ANTIDEPRESSANTS Serotonin norepinephrine reuptake inhibitors... 

FIGURE 30-2. Pain algorithm. AED, antiepileptic drug APAP, acetaminophen NSAID, non-steroidal antiinflammatory drug SNRI, serotonin-norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

There are three approved drugs, venlafaxine (16), duloxetine (17) and milnacipran (18), in the serotonin-norepinephrine reuptake inhibitor (SNRI) class. Whereas milnacipran blocks 5-HT and NE reuptake with almost equal potency, venlafaxine and duloxetine block 5-HT reuptake preferentially [39-41]. Clinical evidence shows that SNRIs have comparable efficacy in the treatment of MDD compared with antidepressants in the SSRI class. An advantage with SNRIs appears to be the ability of alleviating chronic pain associated with, and independent of depression [42-44],... 

In the past decade, other antidepressants have been introduced. Many of these act, at least in part, via serotonin-mediated mechanisms and, as such, have been tested in the treatment of one or more anxiety disorders. These additional antidepressants include two dual serotonin-norepinephrine reuptake inhibitors (SNRIs),... 

A controlled trial of duloxetine (Cymbalta)—like venlafaxine a dual serotonin-norepinephrine reuptake inhibitor—in the treatment of GAD is currently underway. Anecdotal data suggests that nefazodone (Serzone) and mirtazapine (Remeron) may be effective in the treatment of GAD, though no controlled data is available. In addition, recent concerns regarding nefazodone and liver toxicity have limited this medication s utility. Please refer to Chapter 3 for more information regarding these antidepressants. 

Similar observations can be made with regard to the antidepressants introduced in the last 15 years or so. Both SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) represent some quantitative progress from the earlier antidepressants in that they are less toxic, cause fewer medically significant adverse events and support treatment compliance. As is the case for antipsychotics and schizophrenia, the development of these newer antidepressants was not based on fundamentally new insights into the pathophysiology of affective disorders. 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

Two classes of antidepressants act as combined serotonin and norepinephrine reuptake inhibitors selective serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). 

SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS AND TRICYCLIC ANTIDEPRESSANTS... 

FIGURE 7—1. Shown here is the icon of a dual reuptake inhibitor, which combines the actions of both a serotonin reuptake inhibitor (SRI) and a norepinephrine reuptake inhibitor (NRI). In this case, three of the five pharmacological properties of the tricyclic antidepressants (TCAs) (Fig. 6—27) were removed. Both the SRI portion and the NRI portion of the TCA remain however the alpha, antihistamine, and anticholinergic portions are removed. These serotonin/norepinephrine reuptake inhibitors are called SNRIs or dual inhibitors. A small amount of dopamine reuptake inhibition (DRI) is also present in some of these agents, especially at high doses. 

Unit 6 Classical Antidepressants, Serotonin Selective Reuptake Inhibitors and Norepinephrine Reuptake Inhibitors... 

The serotonin-norepinephrine reuptake inhibitors (SNRIs) block reabsorption of both 5-HT and NE. Examples of this class of antidepressant include venlafaxine (Effexor, A.62) and duloxetine (Cymbalta, A.63) (Figure A.19). 

Reuptake Norepinephrine transporter Tricyclic antidepressants (imipramine, f) Tricyclic norepinephrine reuptake inhibitors (desipiamine, ) Selective norepinephrine reuptake inhibitors (reboxetine, ) Dual serotonin/ norepinephrine reuptake inhibitors (venlafaxine, J.)... 

Category Antidepressant, bicyclic Serotonin-norepinephrine reuptake inhibitor Half-life 3-7 hours... 

SCA Second-generation antipsychotic SNRI Serotonin-norepinephrine reuptake inhibitor SSRI Selective serotonin reuptake inhibitor TCA Tricyclic antidepressant TeCA Tetracyclic antidepressant... 

The importance and versatility of the Friedel-Crafts reaction in thiophene chemistry can be seen in the following examples of duloxetine synthesis involving Friedel-Crafts acylations. Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor (SNRI) known for its use as an antidepressant. 

TCA, tricyclic antidepressants muitipie tested inciude amitriptyline, desipramine, imipramine, nortryptiiine, maprotyiine SSRi, seiective serotonin reuptake inhibitors (tested are citralopram, paroxetine, fluoxetine) Venlafaxine, Duloxetine, Miinacipran (seieaive serotonin norepinephrine reuptake inhibitors, SNRis). 

Corynomycollc acid isolated from the cell walls of Cor-ynebacterium sp. or related organisms exhibit immunostimu-lant properties.Duloxetine is a serotonin-norepinephrine reuptake inhibitor used in major depressive disorder, general anxiety disorder, stress urinary incontinence,diabetic peripheral neuropathy, fibromyalgia,and chronic musculoskeletal pain associated with osteoarthritis and chronic lower back pain. Fluoxetine is a serotonin-uptake inhibitor used as an antidepressant and for treatment of anxiety, alcoholism, and bulimia. " ... 

Duloxetine (Scheme 57.11) is an antidepressant drug that acts as a dual serotonin-norepinephrine reuptake inhibitor, the (5)-enantiomer being twice as potent as its counterpart. Both (/ )- and (5)-duloxetine have been prepared from ester (/ )-48, which in turn has been obtained by the DKR of the (3-hydroxynitrile rac-Al using CAL-B and Ru catalyst 3a. ... 

---