The panicogenic effects of cholecystokinin-tetrapeptide are antagonized by L-365,260, a central cholecystokinin receptor antagonist, in patients with panic disorder

Arch Gen Psychiatry. 1994 Jun;51(6):486-93. 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 CCK-tetrapeptide (CCK-4) in patients with panic disorder.

Design: The study employed a double-blind, placebo-controlled, 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Benzodiazepinones / administration & dosage
  • Benzodiazepinones / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Antagonism
  • Female
  • Heart Rate / drug effects
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Panic Disorder / chemically induced*
  • Panic Disorder / diagnosis
  • Panic Disorder / psychology
  • Phenylurea Compounds*
  • Placebos
  • Psychiatric Status Rating Scales
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Receptors, Cholecystokinin / drug effects
  • Severity of Illness Index
  • Tetragastrin* / antagonists & inhibitors
  • Tetragastrin* / pharmacology


  • Benzodiazepinones
  • Phenylurea Compounds
  • Placebos
  • Receptors, Cholecystokinin
  • Tetragastrin
  • L 365260