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)

A wealth of data support a role for serotonin (5-HT) function in the mediation of satiety responses, that are impaired in patients with bulimia nervosa. Testmeal results are presented in which 26 bulimic patients and 17 normal controls were given in randomized, double-blind-fashion, placebo, and the 5-HT agents m-chlorophenylpiperazine (m-CPP, 0.5 mg/kg p.o.) and L-tryptophan (L-TRP, 100 mg/kg i.v.). Three and one-half hours after drug administration, subjects were allowed to eat and lib from a standardized testmeal of 3,500 calories, after which postprandial vomiting was not allowed. M-CPP, but not L-TRP, significantly decreased meal size in the combined group, the controls, and to a lesser extent, the bulimics (P < or = .06). Maximum m-CPP concentrations were inversely correlated to the number of calories consumed in the total group. Following m-CPP, there were significant decreases in carbohydrate, protein, and fat intake in the total group of subjects. There were also trends for decreased carbohydrate and protein intake in the bulimics following m-CPP. There were trends for both m-CPP and L-TRP to reduce fat intake in the controls. Differences in the effects between m-CPP and L-TRP are likely due to differential involvement of 5-HT receptor subtypes at presynaptic and postsynaptic sites. These studies in humans confirm reports in animals that m-CPP decreases food intake, including carbohydrates, protein, and fat in a mixed testmeal.
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PMID:Testmeal responses following m-chlorophenylpiperazine and L-tryptophan in bulimics and controls. 794 45

A greater understanding of the various serotonin receptor subtypes has led to a clearer appreciation of the role of serotonin in gastrointestinal motility, sensation and secretion. Serotonin is definitely involved in the aetiopathogenesis of cisplatin-induced emesis and carcinoid diarrhoea. The application of serotonergic drugs in clinical therapeutics for gut disturbances is presently dominated by the use of 5-HT3 antagonists for acute chemotherapy-induced nausea and vomiting, and the use of substituted benzamides which are 5-HT4 agonists stimulating gut motor function through 5-HT4 neuronal receptors. The best-studied 5-HT4 agonist is cisapride, which has been shown to stimulate motility at several levels of the gut. Cisapride is approved for healing and maintenance treatment of reflux oesophagitis and is used in several countries for the alleviation of symptoms consistent with regional stasis, from dyspepsia to constipation. Carcinoid diarrhoea is a prototypic disease associated with deranged serotonin metabolism, and a rationale for using 5-HT3 or 5-HT4 antagonists is based on the recent appreciation of the important role of impaired gut motor function in carcinoid diarrhoea. In the future, greater understanding of the serotonin receptor subtypes and their role in gut disorders may lead to novel approaches to alleviate increased visceral perception of functional gastrointestinal disorders, to correct changes in colonic capacitance, or to alter gastrointestinal motility that contributes to diarrhoea or constipation. However, at the present time, it must be stressed that these uses are still at an experimental stage and that careful validation and proper controlled studies are still required.
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PMID:Drugs affecting serotonin receptors. 794 60

Considerable progress has been made in the development of means to limit nausea and vomiting arising from cancer chemotherapy. A number of key conceptual advances in the last decade have been critically important. these include recognition of the value of combination antiemetic therapy, identification of important patient- and treatment-related factors predictive of emesis, and appreciation of the importance of serotonin (5-HT) in the pathophysiology of emesis and the value of selective antagonists of the type-3 serotonin receptor. Comparative trials of the 5-HT3 receptor antagonists and classic antiemetic agents have helped define optimal antiemetic approaches in a number of settings. A combination of a 5-HT3 antagonist and dexamethasone is the treatment of choice for patients receiving single- and multiple-day cisplatin. The 5-HT3 antagonists are also effective agents with noncisplatin chemotherapy. Clear-cut superiority to classic antiemetics such as dexamethasone has not been consistently demonstrated, however. Results with the 5-HT3 antagonists in cisplatin-induced delayed emesis have been disappointing to date. The results of ongoing prospective trials should define their role more clearly. At present a combination of metoclopramide and dexamethasone is the treatment of choice in this setting. Results of trials comparing 5-HT3 antagonists are beginning to emerge. Available information suggests no clinically relevant differences in antiemetic efficacy between these agents. Many questions regarding the optimal use of the 5-HT3 antagonists and their integration into clinical practice remain unanswered and are the appropriate focus for additional study.
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PMID:Treatment of chemotherapy-induced emesis in the 1990s: impact of the 5-HT3 receptor antagonists. 800 Jul 24

1. We investigated whether or not pyrogallol, a generator of free radicals, is emetogenic in Suncus murinus, the house musk shrew. Pyrogallol (i.p.) caused dose-dependent emesis in suncus with an ED50 value of 77.3 mg kg-1. At a dose of 128 mg kg-1, all suncus vomited with mean latency of 18.8 +/- 5.2 min and the number of vomiting episodes was 8.6 +/- 2.9. 2. The prophylactic effects of N-(2-mercaptopropionyl)-glycine (MPG), an antioxidant, and tropisetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, were studied. Pyrogallol (128 mg kg-1, i.p.)-induced emesis was prevented by treatment with MPG (i.p.) or tropisetron (s.c.) with ID50 values of 149 mg kg-1 and 117 micrograms kg-1, respectively. 3. Pyrogallol-induced emesis was completely prevented by surgical abdominal vagotomy. 4. The present results indicate that pyrogallol-induced emesis is characteristically very similar to that caused by cisplatin and support the idea that generation of free radicals causes the release of peripheral 5-HT, which stimulates vagal afferent sensory nerves to cause emesis.
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PMID:Induction of emesis in Suncus murinus by pyrogallol, a generator of free radicals. 800 87

The antiemetic effects of granisetron, a selective 5-hydroxy-tryptamine type 3 receptor antagonist, on postoperative nausea and vomiting were studied and compared with placebo and metoclopramide in 60 patients undergoing general anaesthesia for major gynaecological surgery. The patients received a single i.v. dose of either granisetron (3 mg, n = 20) metoclopramide (10 mg, n = 20), or placebo (saline, n = 20) immediately after recovery from anaesthesia. The effects were assessed during the first three and the next 21 hr after recovery from anaesthesia by means of a nausea and vomiting score; 0 = no emetic symptoms, 1 = nausea, 2 = vomiting. The mean scores during 0-3 hr were 0.8, 0.1 and 0.1 after administration of placebo, metoclopramide and granisetron, respectively; the corresponding scores during 3-24 hr were 0.6, 0.5 and 0.1. The scores of the metoclopramide and the granisetron groups were different from the placebo group in the first three hours (P < 0.05). Although there were no differences in the scores during 0-3 hr between the metoclopramide and the granisetron groups, there were differences during 3-24 hr (P < 0.05). It is concluded that granisetron is superior to metoclopramide in the long-term prevention of postoperative nausea and vomiting after anaesthesia.
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PMID:Reduction of postoperative nausea and vomiting with granisetron. 2318 33

The house musk shrew Suncus murinus recently has been introduced for the study of emesis. We investigated the emetic effects of the opioids morphine (0.1-21.5 mg/kg i.p.) and loperamide (0.01-10 mg/kg i.p.) and found a complete lack of emetogenic potential. Nicotine, however, dose dependently induced vomiting in the Suncus with an ED50 of 8.8 mg/kg s.c. and a 100% incidence at 20 mg/kg. This drug-induced vomiting was reduced by morphine or loperamide: ED50 values obtained were 1.2 mg/kg i.p. for morphine and 0.7 mg/kg i.p. for loperamide. Naloxone (2 mg/kg s.c.) antagonised the inhibitory effect of morphine (2 mg/kg i.p.) or loperamide (10 mg/kg i.p.). Serotonin (20 mg/kg s.c.) had less reliable emetogenic potency than nicotine in the Suncus with incidences between 50 and 100%. However, the serotonin-induced vomiting was abolished by morphine and loperamide and this inhibition was antagonised by naloxone. These results suggest that systemically administered opioids are pure antiemetics in Suncus murinus in contrast to other animal models and man. Naloxone antagonism indicates that this antiemetic effect is mediated by opioid receptors.
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PMID:Absence of emetic effects of morphine and loperamide in Suncus murinus. 804 73

Serotonin type 3 receptors are critical for vomiting induced by radiation and cancer chemotherapy. To investigate the mechanisms involved, we analyzed the effects of abdominal visceral denervation using cats. Thresholds for vomiting induced by the serotonin-3 receptor agonist phenylbiguanide varied depending on the order of chronic nerve transections. Lower thoracic vagotomy, splanchnicectomy, and their sequential combination increased thresholds. However, when splanchnicectomy, which causes a large increase in threshold, was followed 14-51 days later by vagotomy, thresholds dropped by an average of 40%. These results demonstrate plasticity in, and potential for modulation of, the emetic reflex.
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PMID:Plasticity of emesis to a 5-HT3 agonist: effect of order of visceral nerve cuts. 806 9

The pharmacological properties of AD-5423 [2-(4-ethyl-1-piper-azinyl)-4- (4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine] were studied in biochemical and behavioral tests. In vitro, AD-5423 bound preferentially to dopamine (DA)-D2 (Ki, 14.8 nM; cf. haloperidol, 8.79 nM; and clozapine, 149 nM) and serotonin (5-HT)-S2 (Ki, 3.98 nM; cf. haloperidol, 26.8 nM; and clozapine, 8.66 nM) receptors. It displayed low affinity for adrenaline (Ad)-alpha-1 (Ki, 56.3 nM) receptors and was virtually devoid of binding to DA-D1 (Ki, 2870 nM), 5-HT-S3, Ad-alpha-2, Ad-beta, muscarine, tau-aminobutyric acid and benzodiazepine receptors. In addition, AD-5423 was only a weak inhibitor of DA, 5-HT and noradrenaline uptake systems. When administered p.o., AD-5423 (0.3-10 mg/kg) increased brain contents of the DA metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in mice and rats and the 5-HT metabolite 5-hydroxyindoleacetic acid in mice. Behaviorally, AD-5423 (0.2-2 mg/kg p.o.) decreased exploratory activity in mice, suppressed conditioned avoidance responding and methamphetamine-induced hyperactivity in mice and rats, antagonized apomorphine-induced gnawing in rats and vomiting in dogs and reduced hostile responses in monkeys. In these effects, AD-5423 was more or less equi-potent to haloperidol. However, AD-5423 (10 mg/kg p.o.), unlike haloperidol, did not antagonize SKF38393-induced vacuous oral movements in rats. Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane in mice and by para-chloroamphetamine in rats were antagonized by AD-5423 at much lower doses (0.5-2 mg/kg p.o.) than those of haloperidol and clozapine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological profile of AD-5423, a novel antipsychotic with both potent dopamine-D2 and serotonin-S2 antagonist properties. 809 23

The experiments on animals (rats and mice) and pigeons have established that buspirone and other serotonin agonists such as 1-(2-pyrimidinyl)-piperazine derivatives such as ipsapirone (TVX Q 7821), levopirone, kampirone, and sepirone have some pharmacological properties which are typical of neuroleptics. The serotonin agonists under study accelerate rat brain dopamine metabolism show their antagonism with apomorphine in the stereotypy and climbing tests in mice, suppress the conditioned avoidance reflex in rats, and eliminate apomorphine-induced vomiting in pigeons. Serotonin agonists, like serotonin, have been shown to stimulate the impulse-dependent release of 3H-dopamine from the slices of the rat nucleus accumbens and striatum. The capacity of buspirone and other serotonin antagonists of modulating dopamine release is not eliminated by 1A/B and 2 serotonin antagonists such as propranolol (3 microM) and metesergide (1 microM), but it is inhibited by ICS 205-930, a selective antagonist of 3HT receptors.
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PMID:[The possible neurochemical mechanisms of the neuroleptic action of buspirone-like serotonin agonists]. 810 56

This paper described an outline of pharmacological studies of 5-HT3 receptor antagonists, mainly on ondansetron, which control nausea and vomiting associated with cancer chemotherapy. Administration of cytotoxic drugs is known to increase serotonin (5-HT) concentrations, and when released, 5-HT provokes the emetic responses via two routes; 1) 5-HT acts as an intrinsic transmitter substance and stimulates the emetic response via 5-HT3 receptors on vagal afferent terminals; 2) 5-HT transmits impulses to the vomiting center via 5-HT3 receptors on the chemoreceptor trigger zone in the area postrema of the central nervous system. 5-HT3 receptor antagonists are thought to exert an antiemetic action by specifically and competitively blocking 5-HT3 receptors.
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PMID:[An outline of 5-HT3 receptor antagonists (1)--In pharmacological actions]. 823 73


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