Effects of the CCK(B) antagonist CI-988 on responses to mCPP in generalized anxiety disorder

Andrew W. Goddard, Scott W. Woods, Roy Money, Atul C. Pande, Dennis S. Charney, Wayne K. Goodman, George R. Heninger, Lawrence H. Price

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

In order to evaluate the effect of the CCK(B) antagonist CI-988 on behavioral, neuroendocrine, and physiologic responses to the mixed; post- synaptic serotonin (5-HT) agonist/antagonist mCPP, 16 patients with a principal DSM-III-R diagnosis of generalized anxiety disorder (GAD) were enrolled in a study that involved two challenge tests. On one day, patients received a single oral dose of CI-988 followed 30 min later by an i.v. infusion of 0.1 mg/kg mCPP. On a second test day patients received placebo CI-988 followed 30 min later by active i.v. mCPP. The sequence of CI-988 was randomly assigned and the testing was conducted in double in -blind fashion. In an initial dose-finding phase (N = 6) with a dose of CI-988 of 25 mg, there were no significant between-test differences in behavioral response to mCPP. Accordingly, the second phase of the study was conducted with a CI-988 dose of 100 mg in another of patients (N = 10). CI-988 (100 mg) was well tolerated and had no significant effects on pretest anticipatory anxiety. There was no significant blunting of the anxiety response to mCPP as a result of CI-988 administration, nor did CI-988 affect physiologic or neuroendocrine measures. Correlations between peak changes in plasma levels of CI-988 and mCPP-induced anxiety in the high-dose patient group were not significant. Overall, these findings did not provide evidence of anxiolytic effects of CI- 988 in patients with GAD. The lack of effect of CI-988 on neuroendocrine and physiological measures further suggests that CI-988's pharmacological effects could be independent of 5-HT function. However, follow-up studies using higher doses of CI-988 are indicated to confirm this preliminary finding as are studies more closely evaluating the interrelationship between CCK and 5- HT function in GAD.

Original languageEnglish (US)
Pages (from-to)225-240
Number of pages16
JournalPsychiatry Research
Volume85
Issue number3
DOIs
StatePublished - Mar 22 1999

Keywords

  • Anxiety
  • Cholecystokinin
  • Serotonin
  • m-Chlorophenylpiperazine

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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    Goddard, A. W., Woods, S. W., Money, R., Pande, A. C., Charney, D. S., Goodman, W. K., Heninger, G. R., & Price, L. H. (1999). Effects of the CCK(B) antagonist CI-988 on responses to mCPP in generalized anxiety disorder. Psychiatry Research, 85(3), 225-240. https://doi.org/10.1016/S0165-1781(99)00015-3