Abstract
The effects of the cholecystokinin-B (CCK-B) receptor antagonist CI-988 on symptoms elicited by the cholecystokinin tetrapeptide (CCK4) were studied in DSM-IIIR patients with panic disorder. The study employed a double-blind, two-period incomplete block design. Patients (n=14) received two different dosages of CI-988 (50 mg or 100 mg) or placebo 2 h prior to an IV bolus injection of CCK4 (20 µg) on two separate occasions. The primary efficacy parameter was the total intensity score on the Panic Symptoms Scale (PSS). Secondary parameters were the number of panic symptoms, time to and occurrence of the first panic symptoms, duration of symptoms, intensity of apprehension and the percentage of patients who did not have a panic attack. The PSS failed to show a statistically significant treatment effect on any of these outcome measures. The average panic rate was 50%, 14.3% and 37.5% after placebo, 50 and 100 mg CI-988, respectively. The differences in panic rate were not statistically significant. The results of this study suggest that CI-988 in doses up to 100 mg is not effective in reducing symptoms of panic anxiety induced by CCK4.
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References
Abelson JL, Nesse RM, Vinik AI (1994) Pentagastrin infusion in patients with panic disorder. II Neuroendocrinology. Biol Psychiatry 36:84–96
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders (DSM-IIIR). APA, Washington DC
Bammert-Adams J, Pyke RE, Costa J, Cutler NR, Schweizer E, Wilcox Ch S, Wisselink PG, Greiner M, Pierce MW, Pande AC (1995) A double blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder. J Clin Psychopharmacol 15:428–434
Bradwejn J, Koszycki D, Shriqui C (1991) Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder. Arch Gen Psychiatry 48:603–610
Bradwejn J, Koszycki D, Payeur R, Bourin M, Borthwick H (1992b) Replication of action of cholecystokinin tetrapeptide in panic disorder: clinical and behavioral findings. Am J Psychiatry 149:962–964
Bradwejn J, Koszycki D (1994) Imipramine antagonism of the panicogenic effects of cholecystokinin tetrapeptide in panic disorder patients. Am J Psychiatry 151:261–263
Bradwejn J, Koszycki D, Couetoux du tertre A, Van Megen HJGM, Westenberg HGM, Den Boer J A, Karkanias C, Haigh J (1994) 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 51:486–493
Bradwejn J, Koszycki D, Paradis M, Reece P, Hilnton J, Sedman A (1995) The effects of CI-988 on cholecystokinin tetrapeptide induced panic symptoms in healthy volunteers. Biol Psychiatry 38:742–746
Costall B, Domeney AM, Hughes J, Kelly ME, Naylor RJ, Woodruff GN (1991) Anxiolytic effects of CCK-B antagonists. Neuropeptides 19 [Suppl.]: 65–73
Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296
Harro J, Vasar E (1991) Cholecystokinin-induced anxiety: how is it reflected in studies on exploratory behaviour. Neurosci BiobehavRev 15:473–477
Hughes J, Boden P, Costall B, Domeney A, Kelly E, Horwell DC, Hunter C, Pinnock RD, Woodruff GN (1990) Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci USA 87: 6728–6732
Kramer MS, Cutler NR, Ballenger JC, Patterson WM, Mendels J, Chenault A, Shrivastava R, Matzura-Wolfe D, Lines C, Reines S (1995) A placebo controlled trial of L 365-260 a CCKB antagonist, in panic disorder. Biol Psychiatry 37:462–466
Lines C, Challenor J, Traub M (1995) Cholecystokinin and anxiety in normal volunteers: an investigation of the anxiogenic properties of pentagastrin and reversal by cholecystokinin receptor subtype B antagonist L 365-260. Br J Pharmacol 39:235–242
Montigny de C (1989) Cholecystokinin tetrapeptide induces panic like attacks in healthy volunteers. Arch Gen Psychiatry 46: 511–517
Powell KR, Barrett JE (1991) Evaluation of the effect of PD 134308 (CI-988), a CCK-B antagonist, on the punished responding of squirrel monkeys. Neuropeptides 19:75–78
SAS (1989) SAS/Stat User’s Guide, Version 6.0, fourth edition, volumes 1 and 2. SAS Institute Inc., Gary, North Carolina
Singh L, Field MJ, Hughes J, Menzies R, Oles RJ, Vass CA, Woodruff GN (1991) The behavioural properties of CI-988 a selective cholecystokinine receptor antagonist. Br J Pharmacol 104:239–245
Singh L, Field MJ, Vass CA, Hughes J, Woodruff GN (1992) The antagonism of the benzodiazepine withdrawal effects by the selective cholecystokinin-B antagonist CI-988. Br J Pharmacol 105:8–10
Thijssen JHH, Van den Berg JHM, Adlercreutz J (1980) Determination of Cortisol in human plasma: evaluation and comparison of seven assays. Clin Chem Acta 100:39–46
Van Megen HJGM, Den Boer JA, Westenberg HGM (1994a) On the significance of cholecystokinin receptors in panic disorder. Prog Neuropsychopharmacol Biol Psychiatry 18:1235–1246
Van Megen HJGM, Westenberg HGM, Den Boer JA, Haigh JRM, Traub M (1994b) Pentagastrin induced panic attacks: enhanced sensitivity in panic disorder patients. Psychopharmacology 114:449–455
Van Megen HJGM, Westenberg HGM, Den Boer J A (1994c) Effect of the selective serotonin reuptake inhibitor (SSRI) Fluvo-xamine on CCK-4 induced panic attacks. CINP 1994. Psycho-pharmacology 10:270
Van Megen HJGM, Westenberg HGM, Den Boer J A (1996a) Effect of the cholecystokinin-B (CCK-B) receptor antagonist L-365, 260 on lactate induced panic attacks in panic disorder patients. Biol Psychiatry (in press)
Van Megen HJGM, Westenberg HGM, Den Boer JA, Kahn RS (1996b) The panic inducing properties of the cholecystokinin tetrapeptide CCK-4 in patients with panic disorder. Eur Neuropsychopharmacol (in press)
Woodruff GN, Hughes J (1991) Cholecystokinin antagonists. Annu Rev Pharmacol Toxicol 31:469–501
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van Megen, H.J.G.M., Westenberg, H.G.M., den Boer, J.A. et al. The cholecystokinin-B receptor antagonist CI-988 failed to affect CCK-4 induced symptoms in panic disorder patients. Psychopharmacology 129, 243–248 (1997). https://doi.org/10.1007/s002130050186
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DOI: https://doi.org/10.1007/s002130050186