Section Review—Central & Peripheral Nervous Systems: Therapeutic Potential of Cholecystokinin-B Antagonists

Abstract

Cholecystokinin (CCK) is a peptide that has actions in both the brain and the periphery. Thus far, the actions of CCK have been attributed to its interactions with two types of receptors: CCK-A and CCK-B. While CCK-A receptors are located predominately in the periphery, CCK-B receptors are located predominantly in the brain and spinal cord. Currently, a strong rationale exists for a role of CCK-B receptors in anxiety. Preclinical and clinical studies have suggested that CCK-B agonists may play a role in the generation of anxiety, and that CCK-B antagonists have anxiolytic-like actions in animals. In addition, CCK-B antagonists are also active in a variety of preclinical tests thought to be predictive of antipsychotic, analgesic, antidepressant, and memory-enhancing effects in man. The first published Phase II studies have shown CCK-B antagonists to be less effective than expected in panic disorder. However, because of bioavailability issues with the tested compounds (i.e., L-365,260 and CI-988), further studies, especially with additional compounds, need to be performed. In addition, controlled clinical tests in schizophrenia, pain, memory loss, and depression still need to be performed.