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Abstract: 5-HT(3) Receptors - fibromyalgia related research

  [ 16 votes ]   [ Discuss This Article ]
www.ProHealth.com • February 18, 2004


Curr Drug Target CNS Neurol Disord. 2004 Feb;3(1):27-37. Costall B, Naylor RJ. Bradford School of Pharmacy, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK. rjnaylor@bradford.ac.uk 5-HT(3)-receptor antagonists are highly selective competitive inhibitors of the 5-HT(3)-receptor with negligible affinity for other receptors. They are potent, rapidly absorbed and easily penetrate the blood-brain barrier; metabolized by the cytochrome P450-system with half-lifes varying from 3-10 hours. The compounds investigated so far do not modify normal behaviour in animals or man and are well tolerated over wide dose ranges, the most common side effects being headache or constipation. Clinical efficacy was first established in chemotherapy-induced emesis (and then in radiotherapy-induced and post-operative emesis), where 5-HT(3)-receptor antagonists set a new standard of antiemetic efficacy and tolerability. The 5-HT(3) receptor antagonists, via a central and / or peripheral action, have been shown to reduce secretion and motility in the gut and possess clinical utility in irritable bowel syndrome, and possibly other visceral pain disorders. Their value in fibromyalgia is being evaluated. In preclinical behavioural assays they induce effects consistent with anxiolysis, improved cognition, anti-dopaminergic activity and use in drug abuse and withdrawal. There is some evidence that ondansetron may reduce alcohol consumption in moderate alcohol abusers but overall, 5-HT(3) receptor antagonists seem to be of limited use in psychiatric disorders: where effects have been seen, they seem to be unusually sensitive to dose and stage of disease. Nevertheless, their antiemetic potential has been of great benefit to cancer patients and the possible extension of their use to bowel disorders may yet fulfil their initial exciting promise. PMID: 14965242 [PubMed - in process]




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