paroxetine, Paxil
Serotonergic markers and lowered plasma branched-chain-amino acid concentrations in fibromyalgia.

Maes M, Verkerk R, Delmeire L, Van Gastel A, van Hunsel F, Scharpe S.

Department of Psychiatry & Neuropsychology, University Hospital of Maastricht, Postbus 5800, 6202 AZ, Maastricht, The Netherlands. crc-mh online.be

The aims of the present study were to examine serotonergic markers, i.e. [3H]paroxetine binding characteristics and the availability of plasma tryptophan, the precursor of serotonin (5-HT), and the plasma concentrations of the branched chain amino acids (BCAAs), valine, leucine and isoleucine, in fibromyalgia. The [3H]paroxetine binding characteristics, B(max) and K(d) values, and tryptophan and the competing amino acids (CAA), known to compete for the same cerebral uptake mechanism (i.e. valine, leucine, isoleucine, phenylalanine and tyrosine), were determined in fibromyalgia patients and normal controls. There were no significant differences in the [3H]paroxetine binding characteristics (B(max) and K(d)) between fibromyalgia and control subjects. There were no significant differences in plasma tryptophan or the tryptophan/CAA ratio between fibromyalgia patients and normal controls. In the fibromyalgia patients, there were no significant correlations between [3H]paroxetine binding characteristics or the availability of tryptophan and myalgic or depressive symptoms. Patients with fibromyalgia had significantly lower plasma concentrations of the three BCAAs (valine, leucine and isoleucine) and phenylalanine than normal controls. It is hypothesized that the relative deficiency in the BCAAs may play a role in the pathophysiology of fibromyalgia, since the BCAAs supply energy to the muscle and regulate protein synthesis in the muscles. A supplemental trial with BCAAs in fibromyalgia appears to be justified.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11104853&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Paroxetine levels in postpartum depressed women, breast milk, and infant serum.

Misri S, Kim J, Riggs KW, Kostaras X.

Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

BACKGROUND: The purpose of this study was to determine the concentrations of paroxetine in maternal serum, breast milk, and infant serum samples and to estimate infant exposure through breastfeeding. METHOD: A total of 25 sample sets was obtained: I sample set each from 23 mother-infant dyads and 2 sample sets from 1 mother-infant dyad. All mothers met DSM-IV criteria for major depressive disorder. The maternal fixed dosage of paroxetine was 10, 20, or 40 mg/day for a minimum of 30 days before the samples were drawn. Samples were collected 6 hours after dose intake, and the concentration of paroxetine in each sample was determined using gas chromatography/mass spectrometry. The analytic method employed in this study is the most sensitive to date, with the ability to detect drug concentrations as low as 0.1 ng/mL. RESULTS: Detectable levels of paroxetine were present in all maternal serum samples and in 24 of the 25 breast milk samples. In all of the infant serum samples, the paroxetine concentrations were below the lower limit of quantification. No unusual adverse effects were reported in any of the infants. CONCLUSION: The results of this study demonstrate that paroxetine, like the other selective serotonin reuptake inhibitors studied to date, is excreted into the breast milk of nursing mothers. The mean infant dose of paroxetine was 1. 1% of the maternal dose. Although no short-term adverse effects were reported in any of the infants in this study, future studies are needed to address a more systematic method for observing and recording any adverse effects. In addition, future studies should incorporate follow-up studies in order to evaluate possible long-term effects of paroxetine exposure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11105735&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Chronic prenatal exposure to paroxetine (Paxil) and cognitive development of mice offspring.

Christensen HD, Rayburn WF, Gonzalez CL.

Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

This study investigated the impact on cognitive development in CD-1 mice from chronic prenatal exposure to the antidepressant paroxetine. CD-1 mice were given either paroxetine as 30 mg/kg/day or a placebo in food bars for 2 weeks before mating and throughout gestation. One offspring per gender from each litter was tested on each of the following tasks: tube runway, spatial maze, passive avoidance chamber, and water straight runway followed by an unforced decision maze. Learning occurred in both genders in all tasks (p<0.001) with no significant differences between treatment groups at the final learning session. Juvenile runway was the only task in which the paroxetine-exposed males demonstrated a learning rate that was slower than the placebo-exposed offspring (p=0.06). Post learning sessions did not show any significant treatment differences during the juvenile and adult periods during the water straight runway, mazes, and avoidance chamber tasks. In conclusion, chronic prenatal exposure in mice of paroxetine did not impact cognition on select tasks.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11106866&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
The influence of buspirone, and its metabolite 1-PP, on the activity of paroxetine in the mouse light/dark paradigm and four plates test.

Hascoet M, Bourin M, Nic Dhonnchadha BA.

Faculty of Medicine and GIS Medicament, JE 2029 Neurobiologie de l'anxiete, Faculte de Medecine BP 53508, 1 rue Gaston Veil, 44035, Nantes, France.

Although numerous animal procedures have been employed in the study of antidepressants (ADs) in anxiety, the results following acute administration remain highly variable. The present study investigated the effect of the SSRI paroxetine (4, 8, and 16 mg/kg, IP) in two tests of anxiety in mice: the light/dark test paradigm, and the four plates test (FPT). In both tests, it was found that paroxetine resulted in an anxiolytic-like effect at doses that did not modify motor performance (at the doses of 4 and 8 mg/kg in the light/dark test and at the doses of 4, 8, and 16 mg/kg in the four plates test). In the light/dark paradigm, both doses of buspirone significantly potentiated paroxetine, while in the four plates only one dose of buspirone (a 5HT(1A) partial agonist) (0.06 mg/kg) increased the anxiolytic-like effect of paroxetine. Prior administration of 1-PP was without effect in the light/dark paradigm but antagonized the effect of paroxetine (at the dose of 0.06 and 0. 5 mg/kg) in the FPT. The results suggested that a balance between pre- and postsynaptic 5-HT(1A) receptor was implicated in the anxiolytic-like effect of paroxetine. Buspirone seemed to emphasize the role of paroxetine in 5-HT(1A) receptor modulation and exerted a biphasic influence in the two tests.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11113483&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Effect of paroxetine on plasma vasopressin and water load testing in elderly individuals.

Marar IE, Towers AL, Mulsant BH, Pollock BG, Amico JA.

Department of Pharmaceutical Sciences Medicine, University of Pittsburgh, Pennsylvania 15261, USA.

Hyponatremia sometimes occurs in elderly depressed patients treated wtih a serotonin reuptake inhibitor (SRI). The cause of the hyponatremia is not yet understood. The objective of this study was to determine the effects of paroxetine, an SRI, on osmoregulated release of vasopressin (also termed antidiuretic hormone) in elderly depressed patients with normal serum sodium. Four women and one man ages 61 to 74 years with a major depressive disorder were administered a water load after they had been treated with a therapeutic dose of paroxetine for 3 to 11 months. Three healthy elderly subjects not receiving paroxetine served as controls. Both the patients and the control subjects excreted > 90% of the ingested water and lowered urine osmolality to < 100 mosmol/kg. We conclude that long-term treatment with paroxetine alone does not appear to affect the ability to excrete a water load or appropriately dilute the urine during a water load (both indices of vasopressin function) in a small group of elderly patients without other risk factors for the development of hyponatremia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11128062&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study.

Meyer JH, Kapur S, Eisfeld B, Brown GM, Houle S, DaSilva J, Wilson AA, Rafi-Tari S, Mayberg HS, Kennedy SH.

Clarke Division, Centre for Addictions and Mental Health, Department ofPsychiatry, University of Toronto, Ontario, Canada. jmeyer camhpet.on.ca

OBJECTIVE: In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT(2A) receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT(2A) receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT(2A) receptors in depressed patients. METHOD: After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [(18)F]setoperone and positron emission tomography to assess 5-HT(2A) receptor binding potential in the patients before and after treatment and in 19 age-matched healthy subjects. RESULTS: 5-HT(2A) binding potential declined with age in all cortical regions in the depressed and healthy subjects. There was a significant interaction between age and treatment effect on 5-HT(2A) binding potential in all cortical regions. Subjects aged 20 to 30 years had a 10% decrease in 5-HT(2A) binding potential after treatment, whereas subjects aged 30 to 40 had no change. No regional differences in 5-HT(2A) binding potential between depressed and healthy subjects were found. CONCLUSIONS: 5-HT(2A) receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT(2A) receptors in the cortex of young patients with depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11136637&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
5-HT1B Autoreceptors limit the effects of selective serotonin re-uptake inhibitors in mouse hippocampus and frontal cortex.

Malagie I, Trillat AC, Bourin M, Jacquot C, Hen R, Gardier AM.

Laboratoire de Neuropharmacologie UPRES EAD MENRT, Faculte de Pharmacie IFR-ISIT Institut de Signalisation et d'Innovation Therapeutique, Universite Paris-Sud, Chatenay-Malabry, France.

We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5-hydroxytryptamine, 5-HT) 1B receptor subtype in mediating the effects of selective serotonin re-uptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5-HT]ext in the ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5-HT]ext in knockout than in wild-type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild-type mice at the 1 mg/kg, but not at 5 mg/kg. In addition, either the absence of the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiated the effect of a single administration of paroxetine on extracellular 5-HT levels more in the ventral hippocampus than in the frontal cortex. These data suggest that 5-HT1B autoreceptors limit the effects of SSRIs on dialysate 5-HT levels at serotonergic nerve terminals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11158258&dopt=Abstract paroxetine, Paxil, Paxil CR