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


METHODS
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.


CONCLUSIONS
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.
Bradwejn
J
J
Department of Psychiatry, McGill University, Montreal, Quebec.
Koszycki
D
D
Couëtoux du Tertre
A
A
van Megen
H
H
den Boer
J
J
Westenberg
H
H
D000284:Administration, Oral; D000328:Adult; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004336:Drug Antagonism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000139:chemically induced* / Q000175:diagnosis / Q000523:psychology; D010671:Phenylurea Compounds; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000187:drug effects; D012720:Severity of Illness Index; D013758:Tetragastrin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D010919:Placebos; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C058121:L 365260