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June 1994

The Panicogenic Effects of Cholecystokinin-Tetrapeptide Are Antagonized by L-365,260, a Central Cholecystokinin Receptor Antagonist, in Patients With Panic Disorder

Author Affiliations

From the Department of Psychiatry, McGill University, Montreal, Quebec (Drs Bradwejn and Couëtoux du Tertre, Ms Koszycki, and Mr Annable), and the Department of Biological Psychiatry, University of Utrecht, the Netherlands (Drs van Megen, den Boer, and Westenberg).

Arch Gen Psychiatry. 1994;51(6):486-493. doi:10.1001/archpsyc.1994.03950060050005

Background:  We investigated whether the selective brain cholecystokinin (CCKB) receptor antagonist, L-365, 260, could antagonize the panicogenic effects of CCKtetrapeptide (CCK-4) in patients with panic disorder.

Design:  The study employed a double-blind, placebocontrolled, two-period crossover design. Patients (N=29) received a single oral dose of L-365, 260 (10 or 50 mg) or placebo 90 minutes prior to injection of CCK-4. After a 1-week washout period, patients received a different dose of L-365,260 or placebo according to a balanced incomplete block design.

Results:  The 50-mg dose of L-365, 260 was superior to placebo in reducing the number (P<.01) and sum intensity (P<.001) of symptoms induced with CCK-4. Panic attack frequency following CCK-4 injection was 88% for patients receiving placebo, 33% for those receiving the 10-mg dose, and 0% for those receiving the 50-mg dose. The difference between the effects of the 50-mg dose and placebo was statistically significant (P=.002). Increases in heart rate following CCK-4 injection were markedly reduced with both the 50-mg (P<.0001) and 10-mg (P<.01) doses compared with placebo.

Conclusion:  These data suggest that CCKB receptors are an important site of action of exogenous CCK-4. It will be important to determine in future studies the efficacy of CCKB receptor antagonists as antipanic agents.