Evaluation and interpretation of dose response experiments with decreased baseline.
Frequently, the effects of a drug are studied in the presence of another drug which decreases the baseline for the action of the first drug. This may pose problems in terms of the evaluation of the action of interaction of one or both of the interacting drugs. When the effect of the interacting drugs (or conditions) are independent, the resulting effects of a drug A at a decreased baseline can be expected to conform to the equation given in this paper. If there is true, interactive antagonism, the resulting effect will not conform to this equation. The consequence of an independent interaction, which is in agreement with the equation given, is that the net effects of A are not affected by B, although B decreases the baseline for the action of A. Hence, the net effects of A are actually independent of (changes in) the baseline, and can best be described by the term "pseudo-antagonism" or "baseline-antagonism". Experimental evidence is provided for such independent antagonistic interventions. These findings also give an explanation for phenomena related to the "law of initial value" (1).
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009241:Ipratropium / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011802:Quinidine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D002217:Carbachol; D009241:Ipratropium; D011802:Quinidine