Clinical–Alimentary TractCondition-specific deactivation of brain regions by 5-HT3 receptor antagonist Alosetron☆,☆☆,★
Section snippets
IBS patients
Patients were required to meet Rome I criteria for IBS,19 and be clinically and endoscopically without inflammatory or other structural intestinal disease. Patients recruited by advertisement and from the UCLA Functional Bowel Center were assessed during a 1-week screening period. Before screening, all patients gave informed consent in compliance with Food and Drug Administration requirements. Subjects were excluded during screening if they had a major psychiatric disorder, or scored >63 on any
Clinical characteristics of the treatment groups
There were no statistically significant differences between the Alos group (n = 20) and the placebo group (n = 17) in age (mean age, 39.2 vs. 40.7 years), gender (% females 45 vs. 53), baseline intensity ratings of IBS symptoms (7.4 ± 1.1 vs. 7.6 ± 1.0; maximum of scale, 20), and bowel habit (% diarrhea-predominance, 65 vs. 47). Baseline symptom ratings were not significantly different in subjects who received Alos at a dose of 1 mg twice daily and those receiving the higher doses of 2–4 mg
Discussion
The main findings of the current study are as follows: (1) Compared with placebo, Alos treatment reduced rCBF in ventromedial PFC, infragenual cingulate, hypothalamus, ventral striatum, and amygdala, all structures of the EMS, most of which contain 5-HT3Rs.12, 26 Drug-induced deactivations were most consistent for the right amygdala, were strongest in the baseline condition, and weakest during the rectal distention. Similarly, deactivation of cortical regions was observed in the 3 scans before,
Acknowledgements
The authors thank Drs. Charles Brown, Dan Silverman, Tony Lembo, Ronnie Fass, and Max Schmulson for help with performance of the studies; to the staff of the PET facilities Francine Aguilar, Priscilla Contreras, Dr. Ali Khonsary, Kristine Coyle, Der-Jen Liu, Larry Pang, Nayda Quinones, Josephine Ribe, and Ron Sumida; to Dr. William Blahd for his support; and to Teresa Olivas for her valuable preparation of the manuscript.
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Address requests for reprints to: Emeran A. Mayer, M.D., CURE Digestive Diseases Research Center/Neuroenteric Disease Program, UCLA Division of Digestive Diseases, GLA VA HS, Building 115, Room 223, 11301 Wilshire Boulevard, Los Angeles, California 90073. e-mail: [email protected]; fax: (310) 794-2864.
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Supported by NIH grants DK 48351 (to E.A.M.), NR 04881 (to B.D.N.), AR 46122 (to L.C.) and funds from Glaxo Wellcome, Inc., Research Triangle Park, North Carolina.
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Dr. Mayer is a member of GSK IBS Advisory Board and has received grants for basic and clinical projects from GSK.