Drugs online research references
Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(5):585-94.
The chronic effects of desipramine and sertraline on platelet and synaptosomal 5HT uptake in olfactory bulbectomised rats.
Butler J, Tannian M, Leonard BE.
Department of Pharmacology, University College, Galway, Republic of Ireland.
1. Depressed patients show a characteristic decrease in the rate of uptake of serotonin into their platelets, which is normalised only by clinically effective antidepressant treatment. 2. We also find a decrease in platelet 5HT uptake rates in the olfactory bulbectomised (OB) rat model of depression, which return to normal following three weeks of treatment with desipramine or sertraline. 3. Synaptosomal 5HT uptake appears to consist of a low affinity, high capacity component and a high affinity, low capacity component, both of which are increased in the OB rat, compared to its sham operated control, and normalised by chronic antidepressant treatment. 4. The low affinity uptake of serotonin is not inhibited by in vitro incubation with sertraline, which suggests that the low affinity system may be associated with a non-specific uptake of 5HT into noradrenergic or dopaminergic nerve endings.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3222448&dopt=Abstract
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Int Clin Psychopharmacol. 1988 Oct;3(4):343-7.
The platelet serotonergic system in depression and following sertraline treatment.
Butler J, Leonard BE.
Department of Pharmacology, University College Galway, Republic of Ireland.
This preliminary study examined the effect of 8 weeks' treatment with the serotonin (5HT) uptake inhibitor, sertraline, on the platelet serotonergic system in depression. Patient pre-treatment platelet 5HT uptake rates and 5HT-mediated platelet aggregation responses were significantly reduced compared to the control values. Binding of the tritiated 5HT2 receptor antagonist, 3H-ketanserin, to platelet membranes from the patient group was increased above control levels. All the patients in the study had recovered from the depressive episode, assessed using the Hamilton depression rating scale, following 8 weeks' sertraline treatment. Eight weeks' sertraline treatment also resulted in a normalization of the biochemical parameters examined. Therefore, we conclude that sertraline is an effective antidepressant and these results confirm previous reports of abnormal platelet serotonin transport and aggregation response as putative markers of the depressed state.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3235819&dopt=Abstract
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Eur J Pharmacol. 1988 Feb 9;146(2-3):299-306.
Kinetics of the interaction of sertraline with the human platelet plasma membrane 5-hydroxytryptamine carrier.
Phillips OM, Wood KM, Williams DC.
Department of Biochemistry, Trinity College, Dublin, Ireland.
Sertraline, a new selective 5-HT uptake inhibitor showed a mixed pattern of inhibition of human platelet 5-HT uptake with a Ki value of 2.5 nM and K'i value of 25 nM. Imipramine and alaproclate were found to be fully competitive inhibitors of 5-HT uptake with Ki values of 8 and 130 nM respectively. Sertraline was a fully competitive inhibitor of high-affinity [3H]imipramine binding to platelet membranes with a Ki value of 1.3 nM, as was alaproclate and 5-HT with Ki values of 170 and 800 nM respectively. Both sertraline and imipramine, at a concentration of 10 microM caused a fast monophasic dissociation of [3H]imipramine from platelet membranes in contrast to serotonin which caused a slow monophasic dissociation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3371401&dopt=Abstract
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