The Transition From Agonist to Antagonist Activity: Symmetry and Other Considerations

Property Distributions: Differences between Drugs, Natural Products, and Molecules from Combinatorial Chemistry

“…This greater rigidity in natural products contributes to their higher selectivity and binding free energy. It may also contribute in some cases to the induction of changes in receptor conformation, which may be important in receptor function, such as agonism-antagonism . Obviously, mimicking this in synthetic compounds would introduce substantial synthetic costs, such as the need for multiple cyclization reactions and the formation of a number of carbon−carbon bonds.…”

Development of ultra short‐acting muscle relaxant agents: History, research strategies, and challenges

“…The concept of conversion of an ''agonist'' to an ''antagonist'' (usually the competitive, or ''surmountable''-type), by applying appropriate structural changes, has been known for several decades; 57,58 and reviewed recently. 59 It has been applied to muscarinic agonists and antagonists, 60 to quaternary ammonium type agents in general 61 and to ganglionic blocking 62,63 and muscle relaxant agents 25 in particular. Among the recognized structural features, leading from an ''acetylcholinergic'' agonist to an antagonist one should first observe the replacement of the small cationic ''head,'' consisting of a trimethyl ammonium terminal group in ACh, by larger alkyl or aralkyl groups and/or surrounding it by an ''umbrella'' like shielding frame (usually in the form of mono or bicyclo-alkane-rings).…”