Plasma and tissue binding of psychotropic drugs
Most pharmacological actions are the result of binding of drug molecules to specific receptors. However, only in a few instances are these receptors known entities which lend themselves to investigation. Thus, the large number of binding studies carried out in recent years rather reflects the fact that there is a multitude of additional drug binding sites, such as metabolic and transport sites, as well as a variety of non-specific sites. The latter are also called ‘silent receptors’ or ‘sites of loss’ since their occupation does not result in pharmacological actions. However, this kind of binding is believed to be a major determinant of pharmacokinetics which again modifies pharmacodynamics.
KeywordsAlbumin Sedimentation Macromolecule Tricyclic Lecithin
Bickel, M. H. (1975). Binding of chlorpromazine and imipramine to red cells, albumin, lipoproteins and other blood components. J. Pharm. Pharmac.
, 733–8CrossRefGoogle Scholar
Bickel, M. H. and Steele, J. W. (1974). Binding of basic and acidic drugs to rat subcellular fractions. Chem.-biol. Interactions
, 151–62CrossRefGoogle Scholar
Di Francesco, C. and Bickel, M. H. (1977). Membrane lipids as intracellular binders of chlorpromazine and related drugs. Chem.-biol. Interactions
, 335–46CrossRefGoogle Scholar
Honegger, U. E., Roscher, A. A. and Wiesmann, U. N. (1980). Is desmethylimip-ramine (DMI) a lysosomotropic agent? Experientia
, 709Google Scholar
Jusko, W. J. and Gretch, M. (1976). Plasma and tissue protein binding of drugs in pharmacokinetics. Drug Metab. Rev.
, 43–140PubMedCrossRefGoogle Scholar
Römer, J. and Bickel, M. H. (1979). Interactions of chlorpromazine and imipramine with artificial membranes investigated by equilibrium dialysis, dual-wavelength photometry, and fluorimetry. Biochem. Pharmac.
, 799–805CrossRefGoogle Scholar
Stegmann, R. and Bickel, M. H. (1977). Dominant role for tissue binding in the first-pass extraction of imipramine by the perfused rat liver. Xenobiotica
, 737–46PubMedCrossRefGoogle Scholar
Weder, H. G. and Bickel, M. H. (1970). Interactions of drugs with proteins. I. Binding of tricyclic thymoleptics to human and bovine plasma proteins. J. pharm. Sci.
, 1505–7PubMedCrossRefGoogle Scholar