Cholecystokinin and anxiety in normal volunteers: an investigation of the anxiogenic properties of pentagastrin and reversal by the cholecystokinin receptor subtype B antagonist L-365,260.
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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Merck Sharp & Dohme Research Laboratories, Terlings Park, Harlow, Essex, UK.
Challenor
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J
Traub
M
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D000328:Adult; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced* / Q000188:drug therapy; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010418:Pentagastrin / Q000008:administration & dosage / Q000009:adverse effects*; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D010418:Pentagastrin