Effects of flumazenil on cholecystokinin-tetrapeptide-induced panic symptoms in healthy volunteers.
The neuropeptide cholecystokinin-tetrapeptide (CCK-4) has potent anxiogenic action in human and animal subjects. On the basis of prior work which demonstrated that benzodiazepine (BZD) receptor agonists antagonized CCK-induced excitation of rat hippocampal neurons we studied whether BZD receptors mediated the anxiogenic effect of CCK-4. To examine this possibility we determined whether the BZD receptor antagonist flumazenil could antagonize the effects of CCK-4 (50 micrograms) in healthy volunteers. Thirty subjects (10 females; 20 males) were pretreated with flumazenil (2 mg in saline) or placebo (0.9% NaCl in water) 15 min prior to CCK-4 challenge in a randomized double-blind crossover design. Flumazenil had no impact on the behavioral and cardiovascular effects of CCK-4, suggesting that BZD receptors do not mediate the anxiogenic action of CCK-4. The influence of GABA and non-GABA-related mechanisms on response to CCK-4 remains to be considered.
Bradwejn
J
J
Psychopharmacology Division, St Mary's Hospital Center, Montreal, Quebec, Canada.
Koszycki
D
D
Couëtoux du Tertre
A
A
Paradis
M
M
Bourin
M
M
D000328:Adult; D000595:Amino Acid Sequence; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005442:Flumazenil / Q000627:therapeutic use*; D058787:GABA-A Receptor Antagonists; D006801:Humans; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D016584:Panic Disorder / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D011963:Receptors, GABA-A / Q000187:drug effects; D013758:Tetragastrin
D058787:GABA-A Receptor Antagonists; D008024:Ligands; D011963:Receptors, GABA-A; D013758:Tetragastrin; D005442:Flumazenil