Uniform characterization of potentiation in simple and complex situations when agents bind to different molecular sites.

Abstract:

: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.

authors

Pöch G,Reiffenstein RJ,Köck P,Pancheva SN

doi

10.1139/y95-217

subject

Has Abstract

pub_date

1995-11-01 00:00:00

pages

1574-81

issue

11

eissn

0008-4212

issn

1205-7541

journal_volume

73

pub_type

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