ABSTRACT

It has been recognized for many years (see Ref. 12 for review) that some antagonists, such as gallamine (52), act allosterically at muscarinic M2 receptors. The initial evidence for an allosteric interaction by gallamine was that the Arunlakshana and Schild plots at myocardial muscarinic M2 receptors exhibited low slopes and curvilinear properties at high antagonist concentrations (50). An allosteric interaction was subsequently shown in radioligand binding studies, where (53) gallamine acted in a negative allosteric fashion or, at least, exhibited a combination of competitive and allosteric antagonism. Similar observations have since been made for stercuronium (54), methoctramikne (55), C7/3' -phthalimidopropyl [heptane-1,7-bis-( dimethyl3'-phthalimidopropy) ammonium bromide) (56), and himbacine (57).