Anxiolyticlike effects of atrial natriuretic peptide on cholecystokinin tetrapeptide-induced panic attacks: preliminary findings.
BACKGROUND
Panic attacks induced by administration of cholecystokinin tetrapeptide (CCK-4) have been evaluated as a valuable tool to investigate the neurobiological mechanisms involved in panic anxiety. The rationale to study the effects of natriuretic peptides on the CCK-4 response is derived from observations that atrial natriuretic peptide (ANP) is released during panic attacks in humans and has anxiolyticlike actions in various animal models.


METHODS
A double-blind, placebo-controlled design was conducted in 9 patients with panic disorder and 9 similar healthy control subjects. After pretreatment with an infusion of 150 microg of ANP or placebo in random order, each subject received 50 microg of CCK-4. Psychopathological parameters as well as physiological measures were sampled before and after CCK-4 administration.


RESULTS
After pretreatment with ANP, the number of CCK-4-induced panic attacks decreased from 8 to 6 in patients and from 5 to 2 in controls. Acute Panic Inventory ratings were significantly reduced in patients after ANP vs placebo pretreatment. Infusion of ANP significantly curtailed the CCK-4-induced release of corticotropin in patients. Heart rate variability analysis indicated a sympathetic stimulation by CCK-4 that was inhibited by ANP in patients and controls.


CONCLUSIONS
The present study indicates that ANP exerts anxiolyticlike effects on CCK-4-stimulated anxiety attacks in patients with panic disorder. In addition, ANP produced an inhibition of the hypothalamopituitary-adrenocortical system and sympatholytic effects.
Wiedemann
K
K
Department of Psychiatry and Psychotherapy, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. wiedeman@uke.uni-hamburg.de
Jahn
H
H
Yassouridis
A
A
Kellner
M
M
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D014151:Anti-Anxiety Agents / Q000097:blood / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D019540:Area Under Curve; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D016584:Panic Disorder / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D010919:Placebos; D011446:Prospective Studies; D013758:Tetragastrin / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D010919:Placebos; D013758:Tetragastrin; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone