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A microdialysis study was undertaken to determine the effect of acute and sub-chronic administration of the selective serotonin reuptake inhibitor, fluvoxamine, and the acute effect of the selective serotonin reuptake inhibitor sertraline, on the naloxone precipitated opioid withdrawal induced increase in hippocampal noradrenaline levels. This study also determined the effect of fluvoxamine and sertraline on opioid withdrawal-induced physical behaviours. Naloxone (1 mg kg(-1); i.p.) increased noradrenaline levels in the hippocampus of morphine dependent rats 20 min after administration, with peak levels of 267+/-13% of baseline, occurring 40 min after administration of naloxone. Opioid withdrawal-induced physical behaviours were evident in morphine dependent rats 5 min after a naloxone injection (1 mg kg(-1); i.p.). Acute fluvoxamine or sertraline (10 mg kg(-1); i.p.) given 40 min before naloxone (1 mg kg(-1); i.p.) did not modify the increased hippocampal noradrenaline levels (242+/-15 and 242+/-19%, respectively), observed in morphine dependent rats following an naloxone injection. Acute fluvoxamine and sertraline (10 mg kg(-1); i.p.) reduced the severity of the naloxone precipitated opioid withdrawal syndrome. Sub-chronic treatment with fluvoxamine (10 mg kg(-1); i.p.) prevented the naloxone precipitated increase in hippocampal noradrenaline levels in morphine dependent rats. Furthermore, sub-chronic fluvoxamine produced a significantly reduced baseline level of noradrenaline in these rats which was 52.5+/-8% of baseline 40 min after naloxone.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12007676&dopt=Abstract
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Biochim Biophys Acta. 2002 May 21;1587(1):92-8.
Antidepressants inhibit human acetylcholinesterase and butyrylcholinesterase activity.
Muller TC, Rocha JB, Morsch VM, Neis RT, Schetinger MR.
Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, RS, Brazil.
This study examines the effect of the antidepressants fluoxetine, sertraline and amitriptyline on cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) activities in human serum and erythrocyte membrane (ghost). The concentrations used range from 3 to 60 microM for fluoxetine and amitriptyline and 0.3 to 12 microM for sertraline. At the micromolar range concentration, different classes of antidepressants, including fluoxetine and sertraline (selective serotonin reuptake inhibitors (SSRIs)) and amitriptyline (tricyclic antidepressant) inhibited human serum cholinesterase. The order of inhibitory potency was sertraline>amitriptyline>>fluoxetine and the IC(50) values were 4.05, 9.43 and 62 microM, respectively. Analysis of kinetic data indicated that the inhibition caused by all the antidepressants was mixed in nature. At the micromolar range concentration, sertraline (60-120 microM) and amitriptyline (60-180 microM) inhibited human erythrocyte AChE. The order of inhibitory potency was sertraline>amitriptyline and the IC(50) values were 80 and 134 microM, respectively. Analysis of kinetic data indicated that the inhibition caused by all the antidepressants in AChE human erythrocyte membrane (ghost) was mixed in nature. The interaction of sertraline with the cholinesterase is labile since the removal of inhibitor by gel filtration recovered completely the enzyme activity. Our results demonstrate that the usual clinical antidepressants are inhibitors of the cholinesterases on human serum and erythrocyte membrane.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12009429&dopt=Abstract
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Prescrire Int. 2002 Jun;11(59):69-72.
Sertraline: new indication. May help children with obsessive-compulsive disorder.
[No authors listed]
(1) The choice of treatment for children with obsessive-compulsive disorder is difficult. Behaviour therapy and antidepressants have not been assessed adequately in this setting, and their efficacy seems limited. Clomipramine was the first antidepressant to show a degree of efficacy. (2) Sertraline is the first drug to be licensed in France for children aged from 6 to 17 years with obsessive-compulsive disorder. (3) According to our literature search, the evaluation file on sertraline in this indication mainly contains data from a double-blind placebo-controlled trial involving 187 children. After 3 months of treatment, sertraline was significantly more effective than placebo, although most children remained symptomatic. Direct comparison is lacking, but sertraline seems as effective as clomipramine. (4) However, 13% of children receiving sertraline left this trial because of adverse events (3% on placebo; p = 0.02). The short-term safety profile of sertraline in children is the same as in adults, i.e. mainly nausea, agitation, headache, insomnia and tremor. (5) We have no data on the effects of prolonged sertraline therapy in children, particularly on neuropsychological development. (6) The first-line treatment of obsessive-compulsive disorder is behaviour therapy. Sertraline, like clomipramine, is an option when behaviour therapy fails or is unfeasible. The choice between sertraline and clomipramine should be discussed case by case, according to their safety profiles; however, we have more experience with clomipramine, which should therefore be preferred over sertraline.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12068839&dopt=Abstract
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