Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alosetron (Lotronex) is a potent, highly selective 5-HT(3) antagonist. Animal models have shown it to be active in anxiety, psychosis, cognitive impairment, emesis and drug withdrawal, though its application in humans has been almost entirely restricted to irritable bowel syndrome (IBS). Alosetron does not cause adverse pharmacodynamic effects, is absorbed rapidly after oral administration and is widely distributed throughout tissues after oral or iv. dosing in animals. Its metabolism is rapid and extensive with N-demethylation, hydroxylation and oxidation. The drug, or its two principal metabolites, is equally excreted through the biliary tract and kidneys. Alosetron has proved safe in a range of toxicity studies; at high repeated dosing, clinical signs were transient and repeated administration produced no significant adverse effects on fertility, reproductive performance or fetal development. In pharmacokinetic studies, bioavailability of alosetron in healthy volunteers is approximately 60% and the plasma half-life is about 1.5 h. There are some gender differences in the pharmacokinetic profile, with 30 - 50% higher alosetron concentrations in females. No consistent differences in alosetron serum concentrations between the young and elderly were observed. The pharmacokinetics of single, oral doses of alosetron are linear up to 8 mg. In human pharmacodynamic studies, alosetron increased basal jejunal water and electrolyte absorption, increased colonic transit time and, consequently, whole gut transit time. Alosetron has been evaluated in two large Phase II trials (randomised, double-blinded, placebo-controlled) and in Phase III trials which included a four-week observation period after cessation. Dose response studies suggested that the effective dosages could be between 1 and 2 mg, twice-daily. In Phase II trials, alosetron, 1 mg b.i.d., resulted in a greater proportion of non-constipated IBS patients reporting adequate relief of pain and discomfort, as well as improvement of bowel symptoms, frequency, urgency and stool consistency when compared with placebo. However, this beneficial effect was seen exclusively among females. Phase III studies evaluated exclusively females with non-constipated IBS and confirmed the results of the Phase II studies. Alosetron was well-tolerated in all studies, with the most frequently recorded adverse event being constipation. Thus, alosetron appears promising in the treatment of abdominal pain and discomfort and normalising of bowel function in patients with non-constipated IBS. It also improves quality of life, has a high degree of tolerability and has an excellent safety profile to date.
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PMID:Pharmacology and clinical experience with alosetron. 1106 Jun 67

Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.
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PMID:Spectrum of use and tolerability of 5-HT3 receptor antagonists. 1551 6