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

Jacques Bradwejn, MD, FRCPC; Diana Koszycki, MA; Anne Couëtoux du Tertre, MD; Harold van Megen, MD; Johan den Boer, MD; Herman Westenberg, PhD; Lawrence Annable, DipStat
Arch Gen Psychiatry. 1994;51(6):486-493. doi:10.1001/archpsyc.1994.03950060050005.
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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.

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