Cytotoxic effects of imipramine on platelets

David J. Goode*, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Incubation for 30 min at 30° with 1 mM imipramine, chlorpromazine or phencyclidine produced increases in creatine phosphokinase (CPK) activity of rat platelet-rich plasma (PRP). Increases in lactic dehydrogenase (LDH) activity of human PRP were produced by imipramine at 0.5 mM. Ouabain, diphenylhydantoin, calcium chloride, EDTA and thrombin did not affect CPK activity of rat PRP. None of the dugs tested except 10 mM diphenylhydantoin affected CPK or LDH activity in platelet-poor plasma. Increases in enzyme activity of PRP produced by 1 mM imipramine were associated with a decrease in platelet count. The increases were independent of temperature of incubation from 0° to 30° and were maximal after a 5-min incubation. The release of LDH and CPK caused by the above drugs is not related to platelet aggregation or the platelet release reaction. The increases in LDH and CPK activity in PRP appear to be the result of platelet destruction or damage to the platelet plasma membrane with release of these enzymes.

Original languageEnglish (US)
Pages (from-to)2629-2635
Number of pages7
JournalBiochemical Pharmacology
Volume23
Issue number18
DOIs
StatePublished - Sep 15 1974

Funding

The present study was designed to investigate the effects of CPZ and imipramine on the release of CPK from rat platelets and lactic dehydrogenase (LDH) from human platelets in vitro. Both enzymes are mainly soluble in the cytoplasm rather than present in organelles. After determining that both drugs could promote release of these enzymes from platelets, the mechanism of the imipramine-induced release of CPK and LDH from platelets was further studied by comparison of its action with agents which promote platelet aggregation and the platelet release reaction, as well * This work was supported by State of Illinois 231-12-RD and USPHS MH 16-1271 Dr. Goode is a recipient of a fellowship from the Foundations Fund for Research in Psychiatry. Dr. Meltzer is the recipient of Research Scientist Development Award MH 47,808. 2629

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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