Cholecystokinin and panic disorder: Past and future clinical research strategies

The involvement of cholecystokinin (CCK) in human anxiety is well documente d. Exogenous administration of CCK-2 receptor agonists, such as cholecystok inin-tetrapeptide and pentagastrin, provoke panic attacks in man. Patients with panic disorder (PD) are hypersensitive. to CCK-2 receptor stimulation compared to healthy volunteers and patients with other anxiety disorders, a nd they differ from healthy subjects in CCK metabolism and genetic characte ristics of the CCK-2 receptor system. This article reviews the corpus of wo rk supporting the role of CCK in anxiety and suggests three research approa ches which can further enhance our understanding of the CCK-2 system in PD. These approaches include: i) searching for a specific anomaly of the CCK-2 receptor system, ii) establishing a relationship between CCK-2 receptor po lymorphism and vulnerability to pharmacologically-induced or spontaneous pa nic attacks, and iii) evaluating the therapeutic efficacy of CCK-2 receptor antagonists which possess adequate pharmacokinetic properties.