5-HT3 Receptors

5-HT3-receptor antagonists are highly selective competitive inhibitors of the 5-HT3-receptor withnegligible affinity for other receptors. They are potent, rapidly absorbed and easily penetrate the blood-brainbarrier; metabolized by the cytochrome P450-system with half-lifes varyingfrom310hours.Thecompounds investigated so far do not modify normal behaviour in animals or man and are well tolerated over wide doseranges, the most common side effects being headache or constipation.Clinical efficacy was first established inchemotherapy-induced emesis (and then in radiotherapy-induced and post-operative emesis), where 5-HT3-receptor antagonists set a new standard of antiemetic efficacy and tolerability. The 5-HT3 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-HT3 receptor antagonists seem to be of limited use in psychiatric disorders: where effects have been seen, theyseem to be unusually sensitive to dose and stage of disease. Nevertheless, their antiemetic potential has beenof great benefit to cancer patients and the possible extension of their use to bowel disorders may yet fulfil theirinitial exciting promise.