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)

This paper is the first to describe aspects of the mechanics of retching in the insectivore Suncus murinus (house musk shrew) and in an animal of such a small size (approximately 50 g). In anaesthetised animals using the novel stimulus of mechanical stimulation of the upper gastrointestinal tract as the provocative stimulus the frequency of retching was found to be about 4 retches/s, a much higher frequency than in other species (dog, cat, ferret). These studies show that quantification of retching in Suncus cannot be undertaken using direct observation. The temporal pattern of the emetic response was characterised in conscious Suncus using motion (1 Hz, 5 min) and nicotine (20 mg/kg s.c.). The ultrapotent capsaicin analogue resiniferatoxin (100 micrograms/kg s.c.) was discovered to be highly emetic and comparative studies showed that nicotine and resiniferatoxin induced the most intense responses with episodes (retches and a vomit) occurring every 10-15 s. The retching response to mechanical stimulation in the anaesthetised Suncus was not blocked by a 5-HT3 receptor antagonist (granisetron, 1-5 mg/kg s.c.), a tachykinin NK1 receptor antagonist (CP-99,994 20 mg/kg s.c. dihydrochloride salt (9+) -(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine) or morphine (2 mg/kg s.c.) but was blocked by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT 100 micrograms/kg s.c.). Suncus appears to be a suitable animal in which to study the pharmacology of the emetic response to mechanical stimulation of the gut. The results are discussed in the light of studies of the pharmacology of emesis in other species.
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PMID:The pharmacology of the emetic response to upper gastrointestinal tract stimulation in Suncus murinus. 883 19

Though antiemetic therapy has improved markedly in the past 15 years, patients still regard nausea and vomiting as two of the most distressing adverse events during chemotherapy. A major progress was the development of the serotonin3 (5-HT3) receptor antagonists. A possible antiemetic effect, achieved by interference with the "serotonergic system", is not restricted to antagonism at 5-HT3 receptors, however, but also includes agonism at 5-HT1A and 5-HT2 receptors, and serotonin synthesis inhibitors. The number of receptors thought to be involved in the emetic reflex has been augmented by neurokinin1 receptors with substance P as the preferred ligand. Animal studies have demonstrated a broad antiemetic profile of substance P antagonists. The somatostatin analogue octreotide has an antiemetic effect in patients with gastrointestinal obstruction, but has not been investigated against chemotherapy-induced emesis. The next few years will disclose, whether the efficacy and safety profiles of one or more of these drugs will make it clinically useful in the treatment of chemotherapy-induced nausea and vomiting.
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PMID:New perspectives in antiemetic treatment. 896 71

LY228729 [(-)-4(dipropylamino)-1,3,4,5-tetrahydrobenz-[c,d]indole-6-carboxa mide]], an agonist at the 5-HT1A subtype of 5-HT receptor, was studied as an antiemetic in pigeons dosed with a highly emetic oncolytic agent, cyclophosphamide. An intramuscular injection of 0.32 mg/kg of LY228729 administered 15 min prior to the intravenous injection of 200 mg/kg of cyclophosphamide totally prevented the acute emetic response induced by cyclophosphamide. When used as a rescue therapy in a separate group of pigeons, LY228729 (0.32 mg/kg, i.m.) prevented further emetic episodes when it was administered after vomiting had already been induced by cyclophosphamide. Injections of LY228729 given at intervals over the next 2 d also attenuated the delayed emetic response induced by cyclophosphamide. LY228729 appears to be a broad spectrum antiemetic agent that is effective against the anticipatory, the acute and the delayed stages of emesis induced by oncolytic agents.
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PMID:Effects of a 5-HT1A receptor agonist on acute and delayed cyclophosphamide-induced vomiting. 953 18

Motion sickness can occur when sensory inputs regarding body position in space are contradictory or are different from those predicted from experience. Signals from the vestibular system are essential for triggering motion sickness. The evolutionary significance of this malady is unclear, although it may simply represent the aberrant activation of vestibuloautonomic pathways that typically subserve homeostasis. The neural pathways that produce nausea and vomiting during motion sickness are presumed to be similar to those that generate illness after ingestion of toxins. The neural substrate of nausea is unknown but may include neurons in the hypothalamus and inferior frontal gyrus of the cerebral cortex. The principal motor act of vomiting is accomplished through the simultaneous contractions of inspiratory and expiratory respiratory muscles and is mediated by neurons in the lateral medullary reticular formation and perhaps by cells near the medullary midline. Cocontraction of the diaphragm and abdominal muscles increases pressure on the stomach, which causes gastric contents to be ejected through the mouth. Effective drugs for combating motion sickness include antihistamines, antimuscarinics, 5-HT1A (serotonergic) receptor agonists and neurokinin type 1 receptor antagonists. However, considerable information concerning the physiological basis and pharmacology of motion sickness is unknown; future research using animal models will be required to understand this condition.
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PMID:Physiological basis and pharmacology of motion sickness: an update. 1005 67

Nausea and vomiting (emesis) occur under a variety of conditions in response to activation of one or more emetic triggers. The act of vomiting is coordinated by neuronal circuitry located in the brain stem between the obex and the retrofacial nucleus, including the region extending from the nucleus of the solitary tract through the lateral tegmental field of the reticular formation to the ventrolateral medulla. The area postrema, medullary midline, and certain higher brain centers are also important for vomiting. The sensation of nausea is thought to involve the cerebral cortex. The most effective near-term treatment for combating nausea and vomiting associated with cyclic vomiting syndrome may come from experimental drugs (NK-1 receptor antagonists, 5-HT1A receptor agonists) or P6 acustimulation, which have been shown to combat nausea and vomiting in response to a broad spectrum of emetic challenges and thus presumably act on central emetic mechanisms.
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PMID:Central mechanisms of vomiting. 1049 38

Several serotonin (5-HT) receptor subtypes have been defined by pharmacological responses to selective agonists and antagonists and by pathways of receptor-effector coupling. Using molecular techniques, additional receptor subtypes have been described. 5-HT receptors are prevalent in the central nervous system and gut and participate in induction of emesis. 5-HT3 antagonists are used to prevent emesis from cancer chemotherapy and also demonstrate efficacy in radiation-induced nausea, postoperative nausea, hyperemesis gravidarum, and nausea and vomiting with the acquired immunodeficiency syndrome. 5-HT4 agonists exhibit prokinetic properties in nauseated patients with gastroparesis and functional dyspepsia. Conversely, 5-HT4 antagonists have antiemetic activity in some experimental models. The 5-HT1D receptor agonist sumatriptan reduces emesis with migraine headaches and in cyclic vomiting syndrome, most likely via action on central nervous system sites. In other models, 5-HT1A and 5-HT2A/5-HT2C agonists exhibit antiemetic properties. The utility of 5-HT receptor ligands in treating emesis is the subject of active investigation.
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PMID:Serotonin receptor physiology: relation to emesis. 1049 49

Significant progress has been made in recent years in developing more effective means of preventing nausea and vomiting induced by cancer chemotherapy. With appropriate application of currently available antiemetic regimens, the majority of patients with cancer who are receiving chemotherapy can anticipate experiencing no emesis during their treatment. Nevertheless, incompletely controlled emesis remains a problem for a significant percentage of patients. Persistent challenges include delayed emesis and emesis following high-dose chemotherapy regimens. The goal of complete prevention of emesis in all patients remains elusive. Therefore, there is a strong rationale for investigating new antiemetic approaches. New antiemetic agents currently under development target the neurotransmitters serotonin (5-hydroxytryptamine; 5-HT) and substance P. A number of new selective antagonists of serotonin 5-HT3 receptors are in clinical trials. Given the lack of clinically significant differences between the available 5-HT3 receptor antagonists, it appears unlikely that any of these new agents will have substantial advantages over currently approved agents. Several other serotonin receptors have been targeted including the 5-HT4, 5-HT1A and 5-HT2A receptors. Of these approaches, only agonism of the 5-HT1A receptor has produced an agent that has proceeded into clinical testing. The most exciting new class of antiemetics currently under development focuses on antagonism of the effects of the neurotransmitter substance P. Results of early clinical trials with tachykinin neurokinin NK1 receptor antagonists demonstrate enhanced control of acute emesis with their addition to currently available agents and promising activity in controlling delayed emesis. Available evidence would strongly suggest that this class of agents will represent the next important advance in efforts to control nausea and vomiting induced by chemotherapy.
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PMID:Antiemetics for cancer chemotherapy-induced nausea and vomiting. A review of agents in development. 1065 96

Ipecac syrup, prepared from a galentical ipecac, contains the nauseant alkaloids cephaeline and emetine. The involvement of receptors and serotonin- and dopamine-metabolizing enzymes in the emesis induced by ipecac syrup and these components was investigated. 1) In ferrets, the selective 5-HT3-receptor antagonist ondansetron (0.5 mg/kg, p.o.) prevented each emesis induced by TJN-119 (0.5 mL/kg, p.o.), cephaeline (0.5 mg/kg, p.o.) and emetine (5.0 mg/kg, p.o.), but the intraperitoneal administration of the selective dopamine D2-receptor antagonist sulpiride failed to significantly suppress the TJN-119, cephaeline and emetine-induced emesis at a dose of 0.1 mg/kg that blocked apomorphine-induced emesis. 2) In the receptor binding assays, cephaeline and emetine had a distinct affinity to 5-HT4 receptor, but no or weak affinity to 5-HT1A, 5-HT3, nicotine, M3, beta1, NK1, and D2 receptors. 3) Cephaeline and emetine did not affect activities of metabolic enzymes of 5-HT and dopamine (MAO-A, MAO-B, tryptophan 5-hydroxylase and tyrosine hydroxylase) in vitro. These results suggest that 5-HT3 receptor plays an important role in the emetic action of TJN-119, cephaeline and emetine, and the 5-HT4 receptor may be involved in their mechanisms.
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PMID:Studies for the emetic mechanisms of ipecac syrup (TJN-119) and its active components in ferrets: involvement of 5-hydroxytryptamine receptors. 1212 Jul 52

The effect of drug acting on 5-HT1A, 5-HT2 and 5-HT3 receptors were studied against cisplatin and apomorphine induced emesis in dogs. Buspirone, 5-HT1A receptor partial agonist significantly reduced the emetic episodes though it had no significant effect on emetic latency. Mianserin, 5-HT2 receptor antagonist exhibited significant reduction in emetic episodes and in latency. Buspirone prevented the apomorphine induced emesis while mianserin had no effect. The antiemetic activity of buspirone may be attributable to its agonistic activity at 5-HT1A receptor and antagonistic activity at dopamine receptors. These findings further confirm the involvement of 5-HT1A and 5-HT2 receptor in cytotoxic drug induced emesis, though the species difference in their antiemetic action can not be ruled out.
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PMID:Involvement of 5-HT1A and 5-HT2 receptor in cisplatin induced emesis in dogs. 1268 22

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of aripiprazole are discussed. Aripiprazole is a third-generation antipsychotic agent indicated for use in the treatment of schizophrenia. Unlike other antipsychotics, aripiprazole demonstrates mixed D2 and serotonin (5-HT1A) receptor agonist-antagonist activity that is hypothesized to improve schlzophrenia's positive and negative symptoms; the drug has been referred to as a dopamine-serotonin stabilizer. Aripiprazole is well absorbed, with peak plasma concentrations occurring within three to five hours after administration. The oral availability is 87%. The mean elimination half-life is about 75 hours for aripiprazole and 94 hours for its active metabolite. In controlled, randomized, multicenter trials, aripiprazole has demonstrated efficacy in the treatment of schizophrenia comparable to that of haloperidol and superior to placebo. In a single clinical trial, aripiprazole was superior to placebo in the treatment of acute mania. The most frequent adverse effects are headache, anxiety, insomnia, nausea, vomiting, and lightheadedness. Because aripiprazole is a substrate of both cytochrome P-450 isoenzymes 3A4 and 2D6, there is a potential for other drugs to affect its metabolism. The recommended starting dosage is 10 or 15 mg daily, preferably administered with meals. Aripiprazole offers an alternative to second-generation antipsychotic agents in the treatment of schizophrenia.
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PMID:Aripiprazole. 1468 20


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