Uniform characterization of potentiation in simple and complex situations when agents bind to different molecular sites.
There is general agreement about potentiation in dose-response studies, characterized by a left shift of the dose-response curve of A by a fixed dose of B when B is causing no effect by itself (simple situation). When B causes an effect similar to A (complex situation) by binding to different molecular sites, we propose an analogous analysis. This approach is based on comparison of experimental effects of A and B in combination with theoretical, independent effects, representing an effect of A that is not affected by B. We argue here that comparison of experimental effects with those of dose-additive (additive) combinations is inappropriate. Theoretical considerations and several practical examples show that the magnitude of effects due to additive combinations widely varies with the slope of dose-response curves of A. Consequently, it is also shown that one and the same theoretical effect may appear overadditive, additive, or underadditive. These situations are demonstrated by the experimental examples: inhibition of cytopathic effects in virus-infected cells, loss of righting reflex in mice, and smooth muscle relaxant effects of organic solvents.
Pöch
G
G
Institute of Pharmacology and Toxicology, University of Graz, Austria.
Reiffenstein
R J
RJ
Köck
P
P
Pancheva
S N
SN
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D002642:Chick Embryo; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D011558:Herpesvirus 1, Suid / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D004364:Pharmaceutical Preparations; D010600:Pharmacology; D004856:Postural Balance / Q000187:drug effects; D012018:Reflex / Q000187:drug effects
D000998:Antiviral Agents; D004364:Pharmaceutical Preparations