Antiplatelet and antileukocyte effects of cardiovascular, immunomodulatory and chemotherapeutic drugs.
In vitro and ex vivo interactions of betaadrenoceptor blocking drugs, antihistamines and chloroquine with blood platelets and polymorphonuclear leukocytes resulted in different alterations of regulatory functions of these blood cells. Inhibition of platelet aggregation, arachidonate regulatory pathway, 5-hydroxytryptamine transportation, removal of platelet membrane receptors, inhibition of second messenger pathways at subcellular level and suppression of phagocytosis are indicative of nonreceptor rather than specific receptor interactions. Binding of drugs with biomembranes is reversible depending on the ionic charge of the molecule and hydrophobicity of the bilayer, partition coefficient, pH and pKa of the amphiphilic molecules and other physico-chemical properties of amphiphilic drugs. Alterations in the drug molecule structure alters the drug-phospholipid binding profile. Any change in the metabolism of membrane phospholipids directly or indirectly influences one or more of the important components of the phospholipid-signalling pathway. In addition to changes in phospholipase A, C and D activities, protein kinase C, calmodulin-phosphodiesterase, Ca2+,Mg2+-ATPase, Na+,K+-ATPase and other messengers were found to be changed in cells and tissue after cationic amphiphilic drug (CAD) administration. Although not much has been understood of the mechanism by which some CAD affect immune functions, there are good reasons to suggest that these effects might occur. CADs share sufficient similarities in their structure even though they come from diverse pharmacological classes. CADs affect ion transport, immune functions, tumour growth, serotonin metabolism and several other functions in the body. Extensive therapeutic use and associated side effects have generated a great deal of interest in understanding the nonreceptor interactions with CADs.
Nosal
Rado
R
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dubravska 9, 841 04 Bratislava, Slovak Republic. exfarano@savba.sk
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D007962:Leukocytes / Q000187:drug effects*; D015427:Reperfusion Injury / Q000517:prevention & control; D013923:Thromboembolism / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D006634:Histamine H1 Antagonists; D002738:Chloroquine