In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner |
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Authors: | Ramadhan Oruch Erlend Hodneland Ian F Pryme Holm Holmsen |
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Institution: | (1) Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway |
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Abstract: | Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs’
intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase
A2 (PLA2) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs
on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA
2
activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining
psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated
between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing
enzymes (PLA2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism.
These effects may be implicated in the psychotropic effects of the drugs and/or their side effects. |
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Keywords: | Human platelets PLA2 MLC PPI cycle Langmuir technique Psychotrophic drugs Diazepam Intercalation Substrate availability |
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