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Research ArticleOriginal Article
Open Access

Effects of psychotropic drugs on the thrombin-induced liberation of arachidonate in human platelets

Ramadhan Oruch, Ian F. Pryme and Holm Holmsen
Saudi Medical Journal October 2008, 29 (10) 1397-1407;
Ramadhan Oruch
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. Tel. +47 (55) 586840. Tel/Fax. +47 (55) 586360. E-mail: [email protected]
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Ian F. Pryme
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. Tel. +47 (55) 586840. Tel/Fax. +47 (55) 586360. E-mail: [email protected]
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Holm Holmsen
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. Tel. +47 (55) 586840. Tel/Fax. +47 (55) 586360. E-mail: [email protected]
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Abstract

OBJECTIVE: To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), clozapine (CLO), haloperidol (HPD), quetiapine (QTP), pimozide (PMZ), and olanzapine (OLP) as well as the tricyclic antidepressants amitriptyline AMI, imipramine IMI, and nortriptyline NTP on thrombin-induced liberation of arachidonic acid AA in platelets.

METHODS: This work was carried out at the Department of Biomedicine, University of Bergen, Norway in 2006-2007. Human platelets pre labelled with [3H] arachidonate were incubated with thrombin in the absence and presence of the drugs, and the amount of free [3H] arachidonate liberated was determined. Myosin light chain (MLC) phosphorylation was determined in [32P] phosphate-labelled platelets after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The effects of the drugs on the molecular area and surface pressure of phospholipid monolayers were determined in the Langmuir apparatus.

RESULTS: All drugs reduced arachidonate liberation with the ranking order of increasing potency: OLP<QTP<HPD<AMI<IMI<PMZ<NTP<CPZ<TFP<PCP. Since phenothiazines are calmodulin antagonists, this property of the drugs was tested as reduction of thrombin-induced phosphorylation of MLC in [32P] Pi-labelled platelets. Only PCP, CPZ, TFP, and NTP reduced MLC phosphorylation. All 11 drugs studied markedly increased the mean molecular area of dipalmitoyl phosphatidylserine monolayers at 37 degrees.

CONCLUSION: The mechanisms for reduction of arachidonate liberation is thought to interfere with activation of cytosolic phospholipase A2 (cPLA2) by alteration of the PLA2 phospholipid substrate structure in platelet membranes.

  • Copyright: © Saudi Medical Journal

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Saudi Medical Journal: 29 (10)
Saudi Medical Journal
Vol. 29, Issue 10
1 Oct 2008
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Effects of psychotropic drugs on the thrombin-induced liberation of arachidonate in human platelets
Ramadhan Oruch, Ian F. Pryme, Holm Holmsen
Saudi Medical Journal Oct 2008, 29 (10) 1397-1407;

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Effects of psychotropic drugs on the thrombin-induced liberation of arachidonate in human platelets
Ramadhan Oruch, Ian F. Pryme, Holm Holmsen
Saudi Medical Journal Oct 2008, 29 (10) 1397-1407;
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© 2025 Saudi Medical Journal Saudi Medical Journal is copyright under the Berne Convention and the International Copyright Convention.  Saudi Medical Journal is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work. Electronic ISSN 1658-3175. Print ISSN 0379-5284.

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