Many classes of drugs that have been successfully used to treat neurological diseases have polypharmaceutical attributes: they affect multiple receptors resulting in both beneficial and unintended effects. One such drug class, the ergot alkaloids, was the basis for methysergide, the first migraine preventive. While the capability to affect multiple receptors likely augmented the therapeutic effect of such compounds, their use was hindered by unintended side effects, such as those associated with agonism at off-target dopaminergic and serotonergic receptors.
Xoc correlated novel receptor activity assessments with observed clinical effects to elucidate which molecular moieties and receptor interactions were responsible for the desired efficacy and unintended side effect profiles.
A new chemical entity, XC101-D13H, and its receptor profile, are discussed as a specific example of a compound with an optimal receptor profile for migraine prevention.