Binding kinetics

In principle, a drug molecule exerts its clinical effect by blocking or activating a disease-related target within the human body for a certain period of time. As the animation depicts, binding of a drug to its target is often a dynamic, reversible process. A drug molecule can bind to its target protein (association) and then, after a given amount of time, will "come off" again (dissociation). It thereby leaves the target protein available for another drug molecule to bind. The time it takes for a drug molecule to bind to and dissociate from its target protein is defined as the drug's binding kinetics. Binding will lead to a series of events (signalling cascade) that ultimately lead to the desired clinical effect (Efficacy), but may also result in undesired and serious side-effects (Safety).

Example of the role of binding kinetics in drug efficacy: Desloratidine
Desloratidine is a Histamine H1 receptor antagonist approved for the treatment of allergy (e.g. hay fever). In retrospect it was shown that the long-lasting effect of desloratidine is the result of a long receptor residence time. An additional advantage is that the drug molecule does not cause drowsiness because it does not readily enter the central nervous system.

Example of the role of binding kinetics in drug safety: Quetiapine
Quetiapine is a Dopamine D2 receptor antagonist approved for the treatment of schizophrenia and bipolar disorder. A problem with the clinical use of Dopamine D2 receptor antagonists is that a slow rate of dissociation can be accompanied by a variety of drug induced movement disorders, such as continuous spasms and muscle contractions, motor restlessness, rigidity and/or irregular, jerky movements. In retrospect it was shown that Quetiapine is a short-acting antipsychotic that combines blocking efficiently the D2 receptors and a faster rate of dissociation, thereby avoiding the aforementioned side-effects.