Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of the 5-HT3 receptor antagonist ondansetron following an 8 mg i.v. dose were investigated in 12 subjects previously phenotyped with debrisoquine. Six subjects were poor metabolisers (debrisoquine metabolic ratios 29-131) and six were extensive metabolisers (debrisoquine metabolic ratios 0.45-3.4). There was no significant difference in AUC, Cmax, CL or t1/2 between the poor and extensive metabolisers. It is concluded that ondansetron clearance is not mediated exclusively by cytochrome P-450 2D6.
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PMID:The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine. 801 61

Tropisetron is a novel, potent and highly selective 5-HT3 receptor antagonist, which is active in the treatment of nausea and vomiting induced by highly emetogenic chemotherapeutic drugs such as cisplatin. Tropisetron selectively blocks the excitation of the presynaptic 5-HT receptors of the peripheral neurones involved in the emetic reflex, and may have other direct actions in the CNS on 5-HT3 receptors, mediating the actions of vagal inputs to the area postrema. Toxicological studies show that tropisetron is generally well tolerated by all animal species investigated and no specific organ toxicity was observed, other than slight loss of body weight development. In man, tropisetron metabolism is linked to the cytochrome P-450 2D6 isoenzyme system, which determines the polymorphism of debrisoquine/sparteine metabolism. As a result, there are phenotypical populations of extensive and poor metabolizers. The two main adverse events in human volunteer tolerability studies with tropisetron were headache and constipation. These adverse events tended to be slightly more intense and to last longer in poor metabolizers, compared with extensive metabolizers. Tropisetron had similar pharmacokinetic characteristics in elderly patients and renal patients, compared with healthy subjects. From a toxicological and pharmacokinetic point of view, therefore, daily doses of 5 mg tropisetron can be administered to both poor and extensive metabolizers, as well as to special populations, without any particular precautions.
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PMID:Pharmacology, toxicology and human pharmacokinetics of tropisetron. 836 93

Nausea and vomiting are 2 of the most upsetting adverse reactions of chemotherapy. Current guidelines propose 5-hydroxytryptamine3 (5-HT3) receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting [chemotherapy-induced nausea and vomiting (CINV)] associated with moderately and highly emetogenic chemotherapy. Meanwhile, both postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting are challenging situations after surgeries and procedures. Prophylactic and therapeutic combinations of antiemetics are recommended in patients at high risk of suffering from PONV and postdischarge nausea and vomiting. Granisetron (Kytril) is a selective 5-HT3 receptor antagonist that does not induce or inhibit the hepatic cytochrome P-450 system in vitro. There are also 4 other antagonists of 5-HT3 receptor (dolasetron, ondansetron, palonosetron, and tropisetron) being metabolized via the CYP2D6 and are subject to potential genetic polymorphism. The launch of a new class of antiemetics, the substance P/neurokinin1 receptor antagonists, was attributed to the scientific update on the central generator responsible for emesis and role of substance P. There has been mounting interest in exploring integrative medicine, either acupuncture or acustimulation of P6 (Nei-Kuwan), to complement the western medicine for prevention and management of nausea and vomiting. The potential application of cannabinoids, either alone or in combination with other agents of different mechanism, could contribute further to improve outcome in CINV. Implementation of future treatment guidelines for more effective management of CINV and PONV could certainly improve the efficacy and outcome of cancer and postoperative care.
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PMID:A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics. 2084 45