# Condition-specific deactivation of brain regions by Alosetron (Lotronex)



## Jeffrey Roberts (Apr 15, 1987)

http://www.ncbi.nlm.nih.gov/entrez/query.f...6&dopt=Abstract Gastroenterology 2002 Oct;123(4):969-977 Related Articles, LinksCondition-specific deactivation of brain regions by 5-HT3 receptorantagonist Alosetron.Berman SM, Chang L, Suyenobu B, Derbyshire SW, Stains J, Fitzgerald L,Mandelkern M, Hamm L, Vogt B, Naliboff BD, Mayer EA.CURE/Neuroenteric Disease Program, Department of Medicine, Physiology,Biobehavioral Sciences and Psychiatry and Brain Research Institute,University of California School of Medicine, Los Angeles, California;University of Pittsburgh Medical Center, MR Research Facility, Pittsburgh,Pennsylvania; Departments of Nuclear Medicine and Psychology, GLA VAHealthcare System, Department of Physics, University of California, Irvine,California; Gastroenterology Clinical Research, Glaxo Wellcome Inc.,Research Triangle Park, North Carolina; and Cingulum NeuroSciencesInstitute, Syracuse, New York.Background & Aims: The 5-HT(3) receptor (5-HT(3)R) antagonist Alosetron(Alos) reduces the symptoms of female patients with diarrhea-predominantirritable bowel syndrome (IBS); yet, the mechanism(s) underlying this effectremains incompletely understood. We determined the effect of Alos onregional cerebral blood flow (rCBF) in the absence and presence of rectal orsigmoid stimulation to evaluate 2 hypothesized mechanisms of therapeuticaction: peripheral antinociception and inhibition of emotional motor system(EMS) regions in the brain. METHODS: Forty-nine nonconstipated irritablebowel syndrome (IBS) patients (26 female) received H(2)(15)O positronemission tomography (PET) brain scans before a randomized,placebo-controlled, 3-week trial with Alos (1-4 mg twice daily). PET scanswere repeated after treatment in 37 completers. We assessed rCBF duringbaseline, rectal distention, and anticipation of undelivered rectaldistention. The 3 conditions were repeated after a series of noxious sigmoiddistentions. Rectal (45 mm Hg) and sigmoid (60 mm Hg) distentions wereperformed with a computer-controlled barostat device. RESULTS: Alostreatment, as compared with placebo, improved IBS symptoms and reduced rCBFin 5-HT(3)R containing regions of the EMS, but not in areas activated bypain. Reduction of rCBF appeared greatest in the absence of visceralstimulation, and was partially reversed by rectal or sigmoid distention.Symptom improvement across sessions was significantly correlated with rCBFdecreases in the 5-HT(3)R-rich amygdala, ventral striatum, and dorsal pons.CONCLUSIONS: Reduction in IBS symptoms correlated with a drug-inducedreduction in the activity of central autonomic networks mediating emotionalexpression that was maximal in the absence of nociceptive input.


----------



## Debbie Benning (Jan 25, 2001)

In other words-it works? I could have told 'em that without all of the big words!


----------



## trbell (Nov 1, 2000)

Jeff, This abstract is somewhat confusing I found out. It seems to imply that lotronex acts like an antidepressant even though Whitehead said in the chat the other night that it doesn't cross the blood-brain barrier?tom


----------



## Kathleen M. (Nov 16, 1999)

I don't know that it has to cross the blood brain barrier to cause a change in the PET scans.IBSers tend to have abnormal responses in the PET scans. This might be due to abnormal stuff being sent from the GI tract nerves (where Lotronex acts) and the brain responding to that abnormal stuff.If Lotronex made the stuff the GI tract nerves send to the brain more normal that could change the PET scans


----------



## trbell (Nov 1, 2000)

PET scans measure brain activity rather than what's there and i think this is what's confusing to some trying to read them. I think for example they don't measure the amount of things like serotonin but the action of it's metaboliztion, for example. in this case i think the scans are measuring the brain's response to the perception of pain in the gut? tom


----------



## Lisa K (Jan 2, 1999)

Hahaha Debbie,my thoughts exactly. Had to read that bulletinmore than once to extract some logical layman's interpretation of "Alosetron affects the brain as well as the gut" Interesting article Jeff, Thanks forbeing so amazingly informative! we appreciate it tremendously. See you at the *party* soon







Lisa K


----------



## Sportster 883 (Feb 11, 2002)

Is Lotronex being used in Canada? Is it on a trial basis or can it be readily prescribed? Is there any link to patients having related heart problems with use of the drug? Does it work for diarrhea, especially when all other methods have been exhausted? I'm bad at returning here so if someone could reply to me at:kgurba###cancom.net Thank you.


----------



## trbell (Nov 1, 2000)

you could check in the lotronex forum. 5HT3tom


----------

