Pharmacological Profile of CGP 48506, A New Positive Inotropic Agent

Abstract

Key Words: Benzodiazocine-Calcium-sensitizing agents-Phosphodiesterase inhibitionPositive inotropy.The purpose of this review is to summarize the studies on the mechanism(s) of action of a new cardiotonic agent, CGP 48506. Cardiotonic drugs are expected to alleviate symptoms of heart failure and reduce mortality of patients suffering from this disease. To put the positive inotropic mechanism(s) of action of CGP 48506 into perspective, some important and well investigated positive inotropic mechanisms are described. The methods used to distinguish the inotropic mechanism(s) of action of CGP 48506 from those of other drugs are briefly discussed. The concept of Ca2+ sensitization by drugs is delineated. Potential advantages and disadvantages of Ca2+ sensitizers for the treatment of heart failure are mentioned. Evidence is presented that CGP 48506 acts primarily as a Ca2+ sensitizer. Data on the effect of CGP 48506 in animal as well as human cardiac preparations indicate that CGP 48506 is a novel and effective positive inotropic agent.

[+]‐EMD 60263—A Novel, Selective, Calcium‐Sensitizing Agent

“…Thus, [+I-EMD 60263 is one of the most selective Ca2' sensitizers known at present. In this context yet another Ca2+ sensitizer has to be mentioned, i.e., the benzodiazocine derivative [+I-CGP 48506 (for review see 19), which is also considered to be devoid of PDE-inhibitory activity. The ICs0 of [+I-CGP 48506 must be >lo00 pM, as this concentration inhibits by only about 30% the type I11 isoenzyme of PDE which is responsible for the positive inotropic effect (18).…”