Ребоксетин

Most of the activity of reboxetine resides in the S,S-isomer(The marketed compound is RR and SS.) It is claimed to besuperior to fluoxetine in severe depression. It is marketed inEurope. At least three tricyclic compounds, desipramine,nortriptyline, and the technically tetracyclic maprotiline areSNERIs. They, of course, have typical characteristic TCAside effects but lower anticholinergic and H₁-antihistaminic(sedative) effects than dimethyl compounds. SNERIs areclinically effective antidepressants.
It would be expected that in the case of SNERIs,α2presynaptic receptors would be desensitized, after whichsustained NE transmission would be via one or more postsynapticreceptors; α1, β1, and β2 receptors are possibilities.

Reboxetine is a nontricyclic SNRI in which the propylamine side chain of the TCAs is constrained into a morpholine ring. It is a potent and selective ligand for the NET, with a mechanism of action is similar to that of desipramine. Reboxetine is used for the treatment of major depressive disorders. It is a chiral compound that is marketed as a racemic mixture of R,R- and S,S-reboxetine. The antidepressant activity for reboxetine appears to reside with the S,S-(+)-enantiomer, which has approximately twofold the inhibition potency of the R,R-enantiomer. It is well tolerated, with different adverse-event profiles, and it appears to be at least as effective as the SSRIs in the treatment of depressive illness. Currently, it is available only in Europe and is under U.S. FDA review. It preferentially inhibits the reuptake of NE (5-HT :NE ratio, 8). Reboxetine is not metabolized by the polymorphic isoforms, CYP2D6 or CYP2C19, and may offer a valuable alternative to the secondary amine TCAs in the treatment of major depression. Reboxetine is likely to become a promising alternative for patients who have failed treatment with or do not tolerate serotonergic antidepressants.

Reboxetine is relatively well tolerated, with insomnia, sweating, constipation, and dry mouth being commonly reported adverse events. Hypotension and urinary hesitancy occur at lower rates than with the TCAs. When compared with the SSRIs, reboxetine is associated with lower rates of nausea, somnolence, and diarrhea.

Reboxetine seems to be an antidepressant that has negligible interference with the pharmacokinetics of other drugs; thus, fewer drug–drug interactions are expected. It also may be possible to use reboxetine in combination with MAOIs, because it has no inhibitory effect on this enzyme, which would avoid tyramineinduced hypertensive reactions.