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The aim of this work was to study whether long-term treatment with fluoxetine could induce peripheral effects by modifying vas deferens contractile activity. For this purpose the contractile response to NE, and 5-HT of vas deferens isolated from male Wistar rats that received fluoxetine 10 mg/kg/day i.p., during 21 days, was studied using the isolated organ bath technique. Results show that vas deferens of treated rats presented spontaneous activity, an effect that was abolished by prazosin and isoproterenol and that was not affected by nitroprusside or indomethacin. In addition, fluoxetine did not modify the response to calcium suggesting that spontaneous activity was not a consequence of an abnormal calcium movement. Fluoxetine induced a significant increase in the response of vas deferens to 5-HT and to low NE concentrations while NE maximal effect was unaffected. Fluoxetine treatment did not modify the binding parameters of [3H]-prazosin to vas deferens. It is concluded that long-term treatment with fluoxetine modifies vas deferens contractile activity. This effect could be the result of an alteration of adrenergic neurotransmission and could account for some of the untoward effects observed during clinical course with fluoxetine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10096441&dopt=Abstract
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J Neurosci. 1997 Nov 1;17(21):8451-8.
Reduced levels of norepinephrine transporters in the locus coeruleus in major depression.
Klimek V, Stockmeier C, Overholser J, Meltzer HY, Kalka S, Dilley G, Ordway GA.
Department of Psychiatry, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
The norepinephrine transporter (NET) is a membrane protein responsible for termination of the action of synaptic norepinephrine and is a site of action of many drugs used to treat major depression. The present study determined whether the binding of [3H]nisoxetine to the NET is altered in the locus coeruleus (LC) in major depression, using brain tissue collected postmortem from subjects diagnosed with major depression and from age-matched normal control subjects. Thirteen of the 15 major depressive subjects studied died by suicide. The distribution of [3H]nisoxetine binding along the rostro-caudal axis of the nucleus was uneven and was paralleled by a similar uneven distribution of neuromelanin-containing cells in both major depressives and psychiatrically normal control subjects. The binding of [3H]nisoxetine to NETs in the midcaudal portion of the LC from major depressive subjects was significantly lower than that from age-matched, normal control subjects. The binding of [3H]nisoxetine to NETs in other regions of the LC was similar in major depressives and control subjects. In contrast to reductions in binding to NETs, there were no significant differences in the number of noradrenergic cells at any particular level of the LC between major depressives and normal control subjects. The decreased binding of [3H]nisoxetine to NETs in the LC in major depression may reflect a compensatory downregulation of this transporter protein in response to an insufficient availability of its substrate (norepinephrine) at the synapse.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9334417&dopt=Abstract
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J Child Adolesc Psychopharmacol. 1997 Summer;7(2):97-107.
Trazodone is only slightly faster than fluoxetine in relieving insomnia in adolescents with depressive disorders.
Kallepalli BR, Bhatara VS, Fogas BS, Tervo RC, Misra LK.
Department of Psychiatry, University of South Dakota School of Medicine, Sioux Falls, USA.
This retrospective chart review examined the relative effectiveness of fluoxetine and trazodone in relieving insomnia associated with depressive disorders in adolescents (aged 13-17 years). We reviewed the hospital charts of consecutively admitted adolescents with a depressive disorder and insomnia, who received one of three treatments: fluoxetine (20 +/- 2.2 mg), trazodone (71 +/- 32 mg), or a fluoxetine-trazodone combination (fluoxetine 29 +/- 2.2 mg, trazodone 68 +/- 29 mg). Each treatment was examined in 20 patients. Insomnia was defined as a change in sleep patterns characterized by decreased total sleep time that was sufficient to cause clinical concern, and insomnia resolution was defined as sleep starting by midnight and lasting 6 hours. Mean time to resolution of insomnia was significantly faster in adolescents treated with trazodone rather than fluoxetine (2.5 vs. 5.1 days, p < 0.05). Trazodone seemed to save only about 3 days and insomnia resolved in all subjects by the 11th day of antidepressant treatment. Median time to insomnia resolution was 2 days (range 1-5 days) in the trazodone group and 4 days (range 1-11 days) in the fluoxetine group. This difference between trazodone and fluoxetine, although statistically significant, was generally not clinically significant in the management of insomnia associated with depressive disorders in adolescents. The resolution of insomnia was not faster for treatment with a combination of fluoxetine and trazodone in comparison to fluoxetine monotherapy. Insomnia resolution was slightly later in older children. These clinical findings await confirmation by a controlled study. Both drugs seemed effective in ameliorating sleep symptoms in this sample, although it is likely that they produced these changes by different mechanisms.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9334895&dopt=Abstract
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