Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers.
A randomized, placebo-controlled, double-blind, three-way crossover design was used to evaluate the effectiveness of single oral 100 mg doses of CI-988, a cholecystokinin B (CCKB) antagonist, in attenuating panic symptoms induced by intravenous injection of cholecystokinin-tetrapeptide (CCK-4). Thirty healthy men received the following treatments on three separate occasions: placebo capsules/placebo, placebo capsules/CCK-4, or CI-988 capsules/CCK-4. There was no marked difference in the number, time to onset, or duration of panic symptoms between CI-988/CCK-4 and placebo/CCK-4. There was, however, a 14% difference in sum intensity scores between these treatments that was statistically significant (p = 0.039). The symptoms most affected by CI-988 were cold chills/hot flushes, chest pain/discomfort, and anxiety/fear/apprehension. Panic attack frequency also decreased following CI-988 treatment (8/30 vs. 16/30; p = 0.035). This decrease, amid otherwise modest effects, could be explained by a preferential effect of CI-988 on the subjective experience of anxiety/fear/apprehension. Possible reasons for the relatively modest effects of CI-988 on CCK-4-induced panic symptoms are discussed.
Bradwejn
J
J
Division of Psychopharmacology, St Mary's Hospital Center, McGill University, Montreal, Quebec, Canada.
Koszycki
D
D
Paradis
M
M
Reece
P
P
Hinton
J
J
Sedman
A
A
D000328:Adult; D000595:Amino Acid Sequence; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008875:Middle Aged; D008969:Molecular Sequence Data; D010200:Panic / Q000187:drug effects* / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D013758:Tetragastrin / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D007211:Indoles; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C065599:PD 134308; D008536:Meglumine