[The basis of non-receptor effects of drugs and biologically active substances]

Most of the cationic amphiphilic drugs (CAD) exert their pharmacological effect through specific receptors which are of protein origin. These interactions result from a sufficiently tight and time dependent binding of CAD to the cell surface transmitting chemical signals into biological effects. For such events each cell is equipped with a wide variety of second messengers. Yet the chemical structure of CAD and biophysical composition of biological membranes enable interactions with corresponding structures without primarily activating the receptor. As a rule such interactions bring about a response characterised as side effect of the individual drug, which might not be equal to the adverse reaction. Nevertheless, these interactions may result also in adverse and toxic responses to the drugs administered. The nonreceptor interactions between CAD, cells, tissues, organs and the whole organism depend on the physico-chemical nature of these drugs and their ability to enter and pass through the plasma membrane on the one side, and on the biological properties of membrane phospholipids and their integral components, on the other. The structure, synthesis, turnover and metabolism of membrane phospholipids play an important role in these processes. Along with A2 and C phospholipases, membrane phospholipids are also donators of the most important second messengers participating in the control of cell functions, such as signal transmission, contraction and relaxation of muscles, cell aggregation, secretion, phagocytosis. CAD are capable to initiate a biological response bypassing specific receptors, interfering thus with the functional structure of membrane phospholipids. This effect is time-dependent and dose-dependent and besides the above mentioned changes in cell functions, CAD can initiate induction of phospholipidoses and nonspecific toxic effects. Further detailed experimental and clinical studies are required to provide full understanding of the interactions between CAD and changes induced in the lipid, protein and carbohydrate cell structures of individual cells and tissues.