The antagnism between cholinomimetic agonists and β-adrenoceptor stimulants the differentiation between functional and metaffinoid antagonism

Allosterism at Muscarinic Receptors: Ligands and Mechanisms

“…Both sets of authors recognised that their observations were consistent with earlier theoretical models of ligand interaction at receptors, referred to as allosteric or metaffinoid interactions [19]. Subsequent radioligand binding studies confirmed and extended the nature of the allosteric interaction of gallamine at muscarinic receptors [20], and an idealised form of the observations is shown in Fig.…”

“…(16) had a potency of ca 100 nM at M 1 receptors but was strongly negatively cooperative with ACh and NMS at all subtypes. In contrast, (19), was a selective and moderately potent allosteric enhancer of both ACh and NMS at M 2 receptors. It was postulated that ring E of (19) was making a specific interaction with the ACh-occupied M 2 receptor.…”

The Inhibitory Effect of Gallamine on Muscarinic Receptors

“…Antagonists which interact at a site which is distinct from but interdependent with the binding sites for agonists and cause a reduction in the affinity of agonists for their binding sites have been discussed by Ariens, Van Rossum & Simonis (1956;1964). Such an effect has recently been termed 'metaffinoid antagonism' (Offermeier & van den Brink, 1974). Like competitive antagonists and unlike noncompetitive antagonists of the 'mectactoid' type (Offermeier & van den Brink, 1974) Figure 5) suggesting that gallamine was reducing the affinity of atropine for its binding sites to a greater extent than it affected the affinity of ACh.…”

“…Such an effect has recently been termed 'metaffinoid antagonism' (Offermeier & van den Brink, 1974). Like competitive antagonists and unlike noncompetitive antagonists of the 'mectactoid' type (Offermeier & van den Brink, 1974) Figure 5) suggesting that gallamine was reducing the affinity of atropine for its binding sites to a greater extent than it affected the affinity of ACh.…”

The Autonomic Nervous System and its Relationship to Tubal Ovum Transport – a Reappraisal

“…In the rabbit oviduct PGEs, which are inhibitory, antagonize the excitatory ef fects of norepinephrine and PGFs, which are excitatory, antagonize the inhibitory effect of isoproterenol [95]. The most likely explanation is functional or physiological antagonism, similar to that of the antagonism of cholinergically-induced contractions by isoproterenol [75], Antagonism probably resides in opposite effects on ionic permeabilities or calcium bind ing. Despite speculation about the role of prostaglandins in modulating autonomic function, information concerning temporal relationships and sites of synthesis is lacking.…”