Cholecystokinin and panic disorder: past and future clinical research strategies.
The involvement of cholecystokinin (CCK) in human anxiety is well documented. Exogenous administration of CCK-2 receptor agonists, such as cholecystokinin-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, and they differ from healthy subjects in CCK metabolism and genetic characteristics of the CCK-2 receptor system. This article reviews the corpus of work supporting the role of CCK in anxiety and suggests three research approaches 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 polymorphism and vulnerability to pharmacologically-induced or spontaneous panic attacks, and iii) evaluating the therapeutic efficacy of CCK-2 receptor antagonists which possess adequate pharmacokinetic properties.
Bradwejn
J
J
Department of Psychiatry, University of Ottawa and the Royal Ottawa Hospital, Ontario, Canada. jbradwej@rohcg.on.ca
Koszycki
D
D
D002766:Cholecystokinin / Q000502:physiology*; D006801:Humans; D016584:Panic Disorder / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D010418:Pentagastrin / Q000633:toxicity; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D012107:Research Design; D013758:Tetragastrin / Q000633:toxicity
D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D002766:Cholecystokinin; D010418:Pentagastrin