Models and methods for studying insurmountable antagonism.

Insurmountable antagonists depress the concentration-response curves of subsequently added agonists. The longevity of the antagonist-receptor complex and the existence of allosteric binding sites are the most frequent explanations for this phenomenon. Yet, observed antagonist behaviour often depends on the tissue, the animal species, the duration of the measured response and the study design. Intact cell studies allow greater flexibility and tighter control of the experimental conditions and therefore have the potential to offer a better insight into the molecular basis of insurmountable antagonism.