Abstract
1. Two studies were undertaken to develop a model of experimentally induced anxiety in normal volunteers based on cholecystokinin (CCK) receptor agonism/antagonism. 2. In Study 1 rapid intravenous injections of the CCK receptor subtype B (CCKB) agonist pentagastrin (0.15, 0.3 and 0.6 micrograms kg-1) were found to produce dose-related increases in subjective ratings of anxiety compared with placebo. 3. In Study 2 the effects of pre-treatment with two doses of the CCKB receptor antagonist L-365,260 (10 mg, 50 mg p.o.) on the anxiety induced by pentagastrin 0.3 micrograms kg-1 i.v. were investigated. Detailed measurements of blood pressure and pulse rate were also undertaken. Pentagastrin produced changes in blood pressure and pulse rate which had a similar time course to that observed for subjective anxiety ratings. L-365,260 reversed both the autonomic and anxiogenic effects of pentagastrin. 4. The pentagastrin model would appear to be a useful tool for investigating potential anxiolytics in normal volunteers.
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Selected References
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- Abelson J. L., Nesse R. M. Cholecystokinin-4 and panic. Arch Gen Psychiatry. 1990 Apr;47(4):395–395. doi: 10.1001/archpsyc.1990.01810160095016. [DOI] [PubMed] [Google Scholar]
- Bock M. G., DiPardo R. M., Evans B. E., Rittle K. E., Whitter W. L., Veber D. E., Anderson P. S., Freidinger R. M. Benzodiazepine gastrin and brain cholecystokinin receptor ligands: L-365,260. J Med Chem. 1989 Jan;32(1):13–16. doi: 10.1021/jm00121a004. [DOI] [PubMed] [Google Scholar]
- Bradwejn J., Koszycki D., Couëtoux du Tertre A., van Megen H., den Boer J., Westenberg H. 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):486–493. doi: 10.1001/archpsyc.1994.03950060050005. [DOI] [PubMed] [Google Scholar]
- Bradwejn J., Koszycki D., Meterissian G. Cholecystokinin-tetrapeptide induces panic attacks in patients with panic disorder. Can J Psychiatry. 1990 Feb;35(1):83–85. doi: 10.1177/070674379003500115. [DOI] [PubMed] [Google Scholar]
- Klerman G. L. Treatments for panic disorder. J Clin Psychiatry. 1992 Mar;53 (Suppl):14–19. [PubMed] [Google Scholar]
- Lesser I. M., Rubin R. T. Diagnostic considerations in panic disorders. J Clin Psychiatry. 1986 Jun;47 (Suppl):4–10. [PubMed] [Google Scholar]
- Rehfeld J. F. Effect of gastrin and its C-terminal tetrapeptide on insulin secretion in man. Acta Endocrinol (Copenh) 1971 Jan;66(1):169–176. doi: 10.1530/acta.0.0660169. [DOI] [PubMed] [Google Scholar]
- Shear M. K. Pathophysiology of panic: a review of pharmacologic provocative tests and naturalistic monitoring data. J Clin Psychiatry. 1986 Jun;47 (Suppl):18–26. [PubMed] [Google Scholar]
- Taylor C. B., Sheikh J., Agras W. S., Roth W. T., Margraf J., Ehlers A., Maddock R. J., Gossard D. Ambulatory heart rate changes in patients with panic attacks. Am J Psychiatry. 1986 Apr;143(4):478–482. doi: 10.1176/ajp.143.4.478. [DOI] [PubMed] [Google Scholar]
- Woodruff G. N., Hughes J. Cholecystokinin antagonists. Annu Rev Pharmacol Toxicol. 1991;31:469–501. doi: 10.1146/annurev.pa.31.040191.002345. [DOI] [PubMed] [Google Scholar]
- van Megen H. J., Westenberg H. G., den Boer J. A., Haigh J. R., Traub M. Pentagastrin induced panic attacks: enhanced sensitivity in panic disorder patients. Psychopharmacology (Berl) 1994 Apr;114(3):449–455. doi: 10.1007/BF02249335. [DOI] [PubMed] [Google Scholar]