Serotonin-norepinephrine reuptake inhibitor drug

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. 

FDA, Combined Use of 5-Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors (SSRIs) or Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) May Result in Life-Threatening Serotonin Syndrome , FDA Public Health Advisory (2006) http //www.fda.gov/Cder/Drug/advisory/ S SRI S S200607.htm... 

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],... 

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). 

SLE systemic lupus erythematosus SLUDGE mnemonic for organophosphate poisoning symptoms Salivation, Lacrimation, Urination, Defecation, Gastrointestinal motility, Emesis SMX sulfamethoxazole SNRIs serotonin-norepinephrine reuptake inhibitors (class of drugs used to treat depression, e.g., venlafaxine)... 

NERVOUS SYSTEM DRUGS ANTIDEPRESSANTS Serotonin norepinephrine reuptake inhibitors... 

Second-generation antipsychotic drug Serotonin-norepinephrine reuptake inhibitor Selective serotonin reuptake inhibitor... 

Drug Class serotonin norepinephrine reuptake inhibitor (SNRI)... 

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. ... 

FIGURE 6-27. Shown here is an icon of a tricyclic antidepressant (TCA). These drugs are actually five drugs in one (1) a serotonin reuptake inhibitor (SRI) (2) a norepinephrine reuptake inhibitor (NRI) (3) an anticholinergic/antimuscarinic drug (Ml) (4) an alpha adrenergic antagonist (alpha) and (5) an antihistamine (HI). 

Duloxetine (LY-248686), (S)-(-i-)-N-methyl-3-(l-naphthyloxy)-3-(2-thienyl)propyl-amine, is expected to be not only a new potent antidepressant but also a NE (norepinephrine) reuptake inhibitor, a 5-HT (serotonin) reuptake inhibitor, and a new treatment drug for stress urinary incontinence [18]. In order to produce an enantiopure key intermediate for the synthesis of the (S)-amine, the Eli Lilly group proposed various strategies [19]. As a result, they selected the enantioseparation of racemic 3-(dimethylamino)-l-(2-thienyl)propan-l-ol with (S)-mandelic acid by diastereomeric salt formation as the most economic and suitable process for industrial-scale production with efficient supporting techniques such as the racemization of the antipode and recycling the recovered materials [20]. However, in the process of demethylation for the preparation of (S)-Duloxetine from (S)-3-(di-methylamino)-l-(2-fhienyl)propan-l-ol, there are some critical problems, such as low yield and considerable decomposition to give impurities. Thus, a direct synthesis of (S)-Duloxetine starting from (S)-3-(methylamino)-l-(2-thienyl)propan-l-ol is expected to be a new route for the production of (S)-Duloxetine. 

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