آراء جديدة في التناقض الذي لا يمكن التغلب عليه

Traditionally classified as surmountable, antagonists that produce parallel rightward shifts of agonist dose-response curves without altering the maximum response produce a misalignment with insurmountable antagonists who also depress the maximum response. Although many studies cite the longevity of the antagonist-receptor complex to explain insurmountable antagonism, alternative explanations such as slowly interconverting receptor conformations, allosteric binding sites, and receptor internalization have been suggested. To complicate matters further, insurmountable antagonism is not solely drug-related; it may also depend on the tissue, species, and experimental design. For drug development purposes, it is crucial to elucidate the molecular mechanisms of insurmountable antagonism. New experimental approaches, such as intact cell studies and the use of computer-assisted simulations based on dynamic receptor models, signal the advent of improved insights in the future.