Drugs online research references
J Urol. 2000 Jun;163(6):1988-91.
Inhibitory effect of serotonergic drugs on contractile response of the rat vas deferens to electrical nerve stimulation: in vivo study.
Kim SC, Seo KK, Han JH, Lee MY.
Department of Urology and Physiology, College of Medicine, Chung-Ang University, Seoul, Korea.
PURPOSE: To evaluate, in vivo, the inhibitory effects of certain serotonergic drugs on the contractile response of the rat seminal tract to electrical stimulation of the hypogastric nerve. MATERIALS AND METHODS: Twenty-five Sprague Dawley rats (250 to 300 gm. each) were equally divided into 5 groups based on experimental agent; normal saline, clomipramine, sertraline, paroxetine, and fluoxetine. The hypogastric nerve was electrically stimulated and the intraluminal pressure of the vas deferens was measured, both pretreatment and 30 minutes after intravenous injection of four different doses (0.1 to 20 x the therapeutic dose) of each agent. Variations of responses relative to the time after administration of each agent (at 10- and 20-fold concentration) were also observed. RESULTS: All serotonergic drugs caused dose-dependent inhibition of elevation in intraluminal pressure of the vas deferens (p <0.05). The inhibitory effect of clomipramine was significantly better (p <0. 05) than that of fluoxetine at a 1-fold dose, while no significant differences were noted among clomipramine, sertraline and paroxetine. At doses of 10- and 20-fold, clomipramine had the strongest inhibitory effect, followed by sertraline and paroxetine, then fluoxetine (p <0.05). No differences were found in the inhibitory effects of the drugs studied, as a function of the time after injection. CONCLUSIONS: Clomipramine was the most potent drug for inhibition of elevation in intraluminal pressure of the rat vas deferens induced by electrical stimulation of the rat hypogastric nerve. The stronger inhibitory effect of clomipramine than the selective serotonin reuptake blockers suggests a possible peripheral action of clomipramine in addition to its central serotonergic action.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10799244&dopt=Abstract
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kumc.edu
BACKGROUND: Indirect evidence suggests that the antidepressant venlafaxine hydrochloride selectively inhibits serotonin (5-HT) uptake at low doses, whereas at high doses, it inhibits both 5-HT and norepinephrine (NE) uptake. We hypothesized that, in vivo, both high and low doses would inhibit the 5-HT uptake of platelets but that the higher dose would differentially blunt the pressor response to tyramine, a marker for NE uptake. METHODS: Healthy male volunteers aged 18 to 45 years received either 75 mg or 375 mg of venlafaxine hydrochloride per day, the 5-HT uptake inhibitor sertraline hydrochloride (50 mg/d), or the NE uptake inhibitor maprotiline hydrochloride (150 mg/d) (n = 8 for each of 4 treatment groups). Changes in platelet 5-HT uptake and the pressor response to intravenous tyramine were assessed following the initial dose and after 1 and 2 weeks of drug administration. RESULTS: Platelet 5-HT uptake was inhibited by venlafaxine across the dose range and by sertraline but not maprotiline. Inhibition was competitive, related to increases in affinity and not related to capacity. Steady-state drug levels were associated with a 5-HT uptake inhibition of 87% or more in subjects taking venlafaxine or sertraline. The pressor response to tyramine differentially distinguished maprotiline from sertraline and the low dose of venlafaxine but not from the high dose of venlafaxine. CONCLUSION: This study provides the first in vivo evidence in healthy humans that both 5-HT uptake and NE uptake inhibition are mechanisms of action sequentially engaged by venlafaxine over its clinically relevant dose range.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10807491&dopt=Abstract
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Depress Anxiety. 2000;11(2):51-7.
Dose of selective serotonin uptake inhibitors across pregnancy: clinical implications.
Hostetter A, Stowe ZN, Strader JR Jr, McLaughlin E, Llewellyn A.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
The use of antidepressants during pregnancy has undergone considerable scrutiny with respect to safety issues, though limited data with respect to dose management and symptom resolution is available. Previous reports on tricyclic antidepressants (TCAs) have demonstrated the need to adjust maternal dose later in pregnancy to maintain therapeutic serum concentrations. However, there is no data on the dosage of selective serotonin uptake inhibitors (SSRIs) required to maintain symptom resolution in women treated for major depression during pregnancy. The purpose of this study, then, was to assess the medication dosage requirements of SSRIs during this time. In this naturalistic study, pregnant women with a primary diagnosis of major depression were followed prospectively through pregnancy at monthly intervals with symptom assessment. Subjects were included in data analysis if they presented prior to 28 weeks gestation, were treated with SSRI monotherapy, received all psychiatric treatment during the pregnancy at the Emory Pregnancy and Postpartum Mood Disorders Program, and achieved euthymia after initial treatment intervention (CGI = 1 and Beck Depression Inventory (BDI) < 9) during pregnancy or failed to respond after eight weeks of treatment. Medication selection was based on personal treatment history or family treatment history (if any), and the published data on SSRIs in pregnancy. All medication dose adjustments were based on depressive symptoms as measured by the BDI and a psychiatric interview (ZNS). Thirty-four pregnant women were included in final analysis. Two thirds of the subjects (n = 22) required an increase in their daily dose of medication to maintain euthymia. The dose increases occurred at 27.1 +/- 7.1 weeks gestation, with mean BDI scores of 16.4 +/- 9.6, compared to a mean treatment response BDI of 6.9 +/- 5.4. Subject's age, education, past personal and familial psychiatric history were not significantly associated with dose adjustment. These novel data on SSRI daily dose in pregnancy parallels the extant literature with tricyclic antidepressants (TCA). Further work to determine the predictors of dose adjustments will provide guidelines for minimizing fetal exposure to both medication and maternal mental illness.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10812529&dopt=Abstract
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