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labopsy.u-bordeaux2.fr
In the rat forced swimming test (FST), reuptake inhibitors selective of either serotonin (5-HT) or noradrenaline (NA) decrease immobility duration, and increase, respectively, swimming and climbing behaviour. In this study, an almost total 6-OHDA-induced NA-depletion prevented the behavioural effects of desipramine, but not fluoxetine. Interestingly, the serotonin/noradrenaline-reuptake-inhibitor milnacipran, as well as a (desipramine+fluoxetine) combination, could produce both swimming and climbing behaviour in NA-lesioned rats, but not in non-lesioned. The new antidepressant mirtazapine, which enhances both 5-HT and NA transmissions, supposedly through the antagonizing of alpha(2)-adrenoreceptors, dose-dependently reduced immobility and increased climbing behaviour. Interestingly, a (mirtazapine+fluoxetine) combination treatment resulted in additive anti-immobility effects and in the summation of fluoxetine-induced swimming with mirtazapine-induced climbing. Taken together, these data suggest that the NA system mediates presynaptic inhibiting interactions on the 5-HT system, that may involve alpha(2)-receptors, and that may limit the efficacy of mixed serotonin/noradrenaline reuptake inhibition in subacute antidepressant treatments.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11872334&dopt=Abstract
note: kwd match prozac online literature
mail.med.upenn.edu
BACKGROUND: Previous studies comparing fluoxetine, paroxetine, and sertraline, the 3 most common selective serotonin reuptake inhibitors (SSRIs), in naturalistic settings have produced conflicting results. With this study, we provide new evidence as to the similarities and differences among these SSRI therapies with respect to the duration of use and health care costs. METHOD: Data from 6 health maintenance organizations were used to identify patients with new-onset major depression. number of days with filled prescriptions, and total health care and depression-related costs. The sample consisted of 1771 patients given initial prescriptions for sertraline (N = 386), fluoxetine (N = 840), or paroxetine (N = 545) in the period from July 1, 1994, to March 31, 1997. Analyses included Cox proportional hazards models (for duration of initial therapy) and ordinary least squares regression (for cost). RESULTS: Patients who initiated therapy with fluoxetine were more likely to have a later interruption of therapy than patients who initiated therapy with sertraline (p = .03) and paroxetine (p = .001). Total 1-year costs did not differ statistically between the treatment groups, but 1-year depression-related costs were significantly lower for patients who initiated therapy with sertraline or paroxetine than for those who initiated therapy with fluoxetine ($332 less for sertraline, 95% confidence interval [CI] = $125 to $562; $339 less for paroxetine, 95% CI = $144 to $416). LIMITATIONS: A limitation of this observational study, as well as of observational studies in general, is that unobserved characteristics of the patients may lead to biased estimates of the impact of treatment on adherence or cost, even with controls for observed characteristics. CONCLUSION: We found no significant differences in total health care costs among the 3 SSRIs, but noted significant differences in depression-related costs (the costs of fluoxetine are greater than those of sertraline and paroxetine). Importantly, there was no relationship between treatment interruption and increased health care or depression-related costs, in contrast to the findings of some, but not all, prior studies.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11874218&dopt=Abstract
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Pharmacogenetics. 2002 Mar;12(2):165-73.
Pharmacological properties of the naturally occurring Ala(457)Pro variant of the human norepinephrine transporter.
Paczkowski FA, Bonisch H, Bryan-Lluka LJ.
Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
Recently, another research group has reported an almost complete loss of function of the human norepinephrine transporter (hNET) in patients who had orthostatic intolerance and who were heterozygous for a guanine to cytosine exchange, resulting in a hNET Ala(457)Pro variant. To explore the reason for the deficiency in NET function, we compared in detail the pharmacology of the Ala(457)Pro variant with that of the wild-type hNET in COS-7 cells transiently transfected with hNET or Ala(457)Pro cDNA. Compared to the wild-type hNET, the Ala(457)Pro variant exhibited a five-fold higher affinity for cocaine, but a two-fold lower affinity for the NET inhibitor nisoxetine, and an unchanged affinity for the antidepressant desipramine. Plasma membrane expression (measured as Bmax of [3H]nisoxetine binding) of the Ala(457)Pro variant was only 40% of that of the wild-type hNET. The Ala(457)Pro variant showed a six- to 10-fold decrease in affinity for the substrates dopamine and 1-methyl-4-phenylpyridinium (MPP(+)). Compared with the wild-type hNET, the maximum rate (V(max)) of norepinephrine uptake by the Ala(457)Pro variant was slightly reduced, whereas the turnover number (calculated from V(max)/B(max)) was approximately two-fold higher. However, the Ala(457)Pro variant exhibited a 50-fold higher K(m) (i.e. lower apparent affinity) for norepinephrine than the wild-type hNET. Thus, the previously reported loss of function of the Ala(457)Pro variant associated with orthostatic intolerance is only partly due to a reduction in plasma membrane expression of the transporter, and is mainly caused by the pronounced reduction in the apparent affinity of norepinephrine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11875370&dopt=Abstract
note: kwd match prozac online literature
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