The selective norepinephrine reuptake inhibitor antidepressant reboxetine: pharmacological and clinical profile - PubMed (original) (raw)

Review

The selective norepinephrine reuptake inhibitor antidepressant reboxetine: pharmacological and clinical profile

Mihály Hajós et al. CNS Drug Rev. 2004 Spring.

Abstract

Reboxetine is the first commercially available norepinephrine reuptake inhibitor developed specifically as a first line therapy for major depressive disorder. In vitro and in vivo pharmacological studies indicated that reboxetine methanesulphonate has high affinity and selectivity for the human norepinephrine transporter over the serotonin and dopamine transporters. Pharmacological specificity is further demonstrated by the absence of affinity for 45 transmitter receptors and CNS targets. Pharmacokinetic studies demonstrated that reboxetine is suitable for twice daily administration (8-10 mg/day) and that it exhibits minimal drug-drug interactions. The starting dose of reboxetine should be reduced in the elderly, in patients with renal or hepatic impairment, or in patients receiving potent CYP3A inhibitors. A total of 20 phase II/III clinical studies comprising placebo-controlled, active comparator-controlled and open-label uncontrolled studies in both short-term and long-term treatment of major depression have been conducted. In the treatment of major depression, reboxetine was superior to placebo in 5 of 12 short- or long-term placebo-controlled studies and was comparable in efficacy to active comparators in 3 out of 3 active-controlled studies. Unlike conventional tricyclic antidepressants (TCAs), reboxetine had only minimal sedative and cardiovascular liabilities, probably due to increased pharmacological specificity of reboxetine as compared with TCAs. Unlike serotonin reuptake inhibitors, this selective and specific norepinephrine reuptake inhibitor demonstrated a distinct side-effect profile with diminishing sexual dysfunction and GI side effects. The availability of this agent has afforded patients suffering from major depressive disorder a new class of agents to combat the debilitating consequence of this psychiatric disease. The demonstrated pharmacological specificity of this compound has provided the psychopharmacology community with a tool to elucidate the role of norepinephrine in brain functions. Testing this agent in different animal models has enabled the exploration of the role of modulation of norepinephrine tone in the therapy of CNS disorders beyond depression.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Andreoli V, Caillard V, Deo RS, Rybakowski JK, Versiani M. Reboxetine, a new noradrenaline selective antidepressant, is at least as effective as fluoxetine in the treatment of depression. J Clin Psychopharmacol 2002;22:393–399. - PubMed
    1. Aston‐Jones G, Rajkowski J, Cohen J. Role of locus coeruleus in attention and behavioral flexibility. Biol Psychiatry 1999;46:1309–1320. - PubMed
    1. Avenoso A, Facciolà G, Scordo MG, et al. No effect of the new antidepressant reboxetine on CYP2D6 activity in healthy volunteers. Ther Drug Monit 1999;2:577–579. - PubMed
    1. Ban TA, Gaszner P, Aguglia E, et al. Clinical efficacy of reboxetine: A comparative study with desipramine, with methodologic considerations. Hum Psychopharmacol 1998;13:S29–S39.
    1. Benmansour S, Cecchi M, Morilak DA, et al. Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level. J Neurosci 1999;19:10494–10501. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources