History And Discovery

Research has implicated dysregulation of serotonin (5-HT) in mood and anxiety disorders. Despite the effectiveness of the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), which exert their effects by inhibiting the enzymatic degradation and reuptake of monoamines, respectively, side effects and potential serious adverse events limited their utility. Researchers thus identified compounds that are selective in blocking neurotransmitter reuptake and yet have little agonist and antagonist activity at receptors thought to be associated with adverse effects. Sertraline [(+)-c/s-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-W-methyl-1-naphthylamine], a naphthylamino compound that is structurally different from MAOIs and TCAs (Figure 14-1), is one of this class of drugs (Guthrie 1991; Heym and Koe 1988).

For the 12 months ending June 2006, it has been estimated that sales of sertraline (under the brand name Zoloft) in the United States exceeded $3 billion (Rancourt 2006). In August 2006, a generic formulation of sertraline became available in the United States, and within the first 2 weeks of its availability, the substitution rate exceeded 77% (Block 2006).

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