Regulatory Effects of Reboxetine Treatment Alone, or Following Paroxetine Treatment, on Brain Noradrenergic and Serotonergic Systems
by
Gould GG, Pardon MC, Morilak DA, Frazer A.
1Department of Pharmacology,
University of Texas Health Science Center at San Antonio,
San Antonio, TX, USA.
Neuropsychopharmacology. 2003 Jun 25


ABSTRACT

When patients do not respond to an initial antidepressant, one clinical approach is to switch to an agent in a different pharmacological class. However, few studies have examined the neurochemical consequences of this practice. To study this, we examined changes in binding sites in rat brain for norepinephrine (NET) and serotonin transporters (SERT), alpha(1), alpha(2), and beta(1) adrenergic receptors after chronic administration of paroxetine (PRX), reboxetine (RBX), or PRX followed by RBX. We also examined the effects of these treatments on mRNA expression for tyrosine hydroxylase (TH). RBX treatment for 3 weeks reduced NET binding significantly, by approximately 40% in terminal field areas, and 6 weeks of RBX reduced it even more, by approximately 60%. RBX treatment for 3 and 6 weeks reduced beta(1) adrenergic receptor-binding sites equally, by 50-60%. At no time did RBX treatment reduce SERT-binding sites. PRX treatment had no effect on beta(1) adrenergic or NET-binding sites, but reduced SERT-binding sites by 75-80%. Neither treatment altered mRNA for TH, alpha(1), or alpha(2) adrenergic receptor-binding sites. When 3 weeks of RBX treatment followed 3 weeks of PRX treatment, NET-binding sites were reduced to the same extent as measured after 6 weeks of RBX treatment alone, indicating that PRX pretreatment may have 'primed' the subsequent regulatory effect of RBX on the NET. Thus, pretreatment of rats with PRX actually enhanced at least one regulatory effect of RBX treatment on the noradrenergic system, and did not interfere with any other pharmacological effect caused by RBX treatment.


Efficacy
Reboxetine
Noradrenaline
NARIs and SSRIs
Dopamine reuptake inhibition
Reboxetine and major depression
Reboxetine and social functioning
Paroxetine (Paxil, Seroxat, Aropax)
Depression, antidepressants and noradrenaline
Reboxetine (Edronax, Vestra) and social functioning




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