Graphic representation of pharmacology: Development of an alternative model

Introduction: Providing clinicians with an easy to grasp and understandable representation of pharmacology is important to allow optimal clinical decisions to be made. Two of the most clinically relevant dimensions are receptor binding affinity and functional activity. The binding affinity for an agonist is described by the dissociation constant (K_A ), and an antagonist by the inhibition constant (K_i ). Functionally, medications can act as superagonists, agonists, partial agonists, antagonists, partial inverse agonists, or inverse agonists at several receptor sites, transporters, or ion channels. Comprehending the differences between agents is complicated by the number and types of binding sites.

Methods: Binding and functional data are obtained from primary literature, product labels, human cloned receptor binding, and other sources. Binding affinities are converted into ratios relative to the putative primary receptor for that category of agent. Antipsychotic binding is referenced to dopamine type 2 long (D2L) receptor binding. Binding affinity ratios (BARs) generate a 6-spoked diagram, with D2L as the hub. The most avidly bound sites are the spokes, and the disk diameter represents the BAR. Where functional data are available, they are shown as a pie chart shading the binding site's disk.

Results: Binding and function diagrams are shown for the antipsychotics where binding data are available and are compared to previous methods of pharmacologic comparisons of antipsychotics.

Discussion: Use of graphic models of psychotropic pharmacology improves clinician comprehension and may serve as an aid to improve rational therapeutics and patient outcomes.