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

The involvement of 5-hydroxytryptamine (5-HT) with cisplatin-induced emesis in the ferret was investigated using reserpine, para-chlorophenylalanine and fenfluramine. Pretreatment with reserpine (5 mg/kg, 24 hr), fenfluramine (5 mg/kg, 4 days) or para-chlorophenylalanine (100 or 400 mg/kg, 4 days) antagonised cisplatin-induced emesis. All treatments reduced the levels of 5-HT in the area postrema and at other cerebral sites, but whilst this action was relatively selective for small doses of para-chlorophenylalanine [only modest effects on noradrenaline (NA) and no change in the content of dopamine (DA) in the area postrema], other treatments reduced levels of dopamine and noradrenaline. Data are discussed in terms of an involvement of 5-HT/catecholamines in the area postrema with the mediation of emesis induced by cisplatin.
 ...
PMID:Reserpine, para-chlorophenylalanine and fenfluramine antagonise cisplatin-induced emesis in the ferret. 290 84

The effects of the putative selective dopamine D-1 antagonist benzazepine SCH 23390 and of the selective dopamine D-2 antagonist Ro22-2586 on stereotypy induced by the selective D-2 agonist RU24213 were compared. RU24213 (0.5-15 mg/kg) dose-dependently induced stereo-typed behaviour characterised by continuous downward sniffing and locomotion. These responses were antagonised, as expected, by 40-200 micrograms/kg Ro22-2586, but surprisingly blocked by 40-200 micrograms/kg SCH 23390. The selectivities of these compounds for dopamine receptor subtypes were verified in terms of their relative abilities to displace the in vitro binding of 3H-piflutixol to striatal D-1 receptors and of 3H-spiperone to D-2 receptors. As SCH 23390 fails to influence D-2 mediated prolactin secretion or emesis in vivo, there appears to be no significant formation of an active metabolite of SCH 23390 with D-2 antagonist activity. Because SCH 23390 has some affinity for 5-hydroxytryptamine receptors, any effect on the serotonergic behavioural syndrome induced by 10 mg/kg 5-methoxy-N,N-dimethyltryptamine was also studied. The serotonergic responses of hind limb abduction, reciprocal forepaw treading and Straub tail were unaltered after 40-200 micrograms/kg SCH 23390, indicating no significant 5-HT blockade or non-specific depressant action at these doses which might influence the expression of stereotypy. Thus, these data are consistent with blockade of tonic D-1 dopaminergic activity that may influence the expression of behaviours initiated by D-2 dopaminergic stimulation.
 ...
PMID:Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2 agonist RU24213. 293 58

The substituted benzamide derivatives, dazopride and metoclopramide, enhanced field stimulation-induced contractions of guinea-pig stomach strips and gastric emptying in the guinea-pig after peripheral, intracerebroventricular and intrahypothalamic injection. In the isolated vagal nerve preparation from the rabbit, both compounds were shown to be 5-hydroxytryptamine M-receptor antagonists. Dazopride and metoclopramide were equipotent in antagonising cisplatin-induced emesis in the ferret, whereas metoclopramide was approximately 200 times more potent than dazopride in antagonising the emesis caused by the dopamine agonist 2-di-n-propylamino-5,6-dihydroxytetralin in the marmoset. In behavioural tests which indicate dopamine receptor antagonism in the rat, metoclopramide induced catalepsy, antagonised amphetamine-induced stereotypy and the hyperactivity induced by the intrastriatal injection of dopamine, caused body asymmetry on unilateral injection into the striatum and also antagonised apomorphine-induced climbing and circling behaviour in the mouse. In contrast, dazopride had little or no action in these tests and failed to displace [3H]spiperone in radioligand binding assays. The use of dazopride provides evidence to dissociate a dopamine receptor blockade from an ability to facilitate gastric emptying and to antagonise cisplatin-emesis, and indicates that antagonism of 5-hydroxytryptamine M-receptors is the essential basis of action for dazopride and plays an important role in the actions of metoclopramide.
 ...
PMID:The action of dazopride to enhance gastric emptying and block emesis. 311 64

The involvement of 5-hydroxytryptamine (5-HT) 5-HT3 receptors in the mechanisms of severe emesis evoked by cytotoxic drugs or by total body irradiation have been studied in ferrets. Anti-emetic compounds tested were domperidone (a dopamine antagonist), metoclopramide (a gastric motility stimulant and dopamine antagonist at conventional doses, a 5-HT3 receptor antagonist at higher doses) and BRL 24924 (a potent gastric motility stimulant and a 5-HT3 receptor antagonist). Domperidone or metoclopramide prevented apomorphine-evoked emesis, whereas BRL 24924 did not. Similar doses of domperidone did not prevent emesis evoked by cis-platin or by total body irradiation, whereas metoclopramide or BRL 24924 greatly reduced or prevented these types of emesis. Metoclopramide and BRL 24924 also prevented emesis evoked by a combination of doxorubicin and cyclophosphamide. These results are discussed in terms of a fundamental role for 5-HT3 receptors in the mechanisms mediating severely emetogenic cancer treatment therapies.
 ...
PMID:Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis. 331 Nov 9

In unanesthetized cats the emetic action of an injection of nicotine into the cerebral ventricle through chronically implanted cannulae was investigated. Nicotine injected in doses of 0.02-1.0 mg produced dose-dependent vomiting, which was abolished after ablation of the area postrema. However, copper sulfate given intragastrically evoked vomiting in cats with an ablated area postrema. The emetic response to intracerebroventricular (ICV) nicotine as well as the vomiting produced by intragastric copper sulfate was depressed or abolished in cats pretreated with ICV reserpine. On the other hand, the emetic response to ICV nicotine and to intragastric copper sulfate was virtually unchanged in cats pretreated with ICV 6-hydroxydopamine and 5,6-dihydroxytryptamine. The duration of vomiting produced by intragastric copper sulfate, but not that of ICV nicotine, was potentiated in cats pretreated with hemicholinium-3. Ganglionic blocking agents, mecamylamine and hexamethonium, injected ICV prevented the vomiting elicited by ICV nicotine. On the other hand, selected anti-muscarinic drugs, alpha and beta adrenergic receptor antagonists, dopamine antagonists, antihistamines and a 5-hydroxytryptamine antagonist all injected into the cerebral ventricle had virtually no effect on the vomiting induced by ICV nicotine. It is postulated that nicotine evokes vomiting by its action on nicotinic receptors within the area postrema but not on catecholaminergic or serotonergic neurones. Finally, acetylcholine could also be involved in the inhibition of the complex mechanisms underlying the central regulation of vomiting.
 ...
PMID:Further studies on nicotine-induced emesis: nicotinic mediation in area postrema. 360 20

MDL 72222, the selective 5-hydroxytryptamine (5-HT) M-receptor antagonist, prevented or reduced cisplatin-induced emesis in ferrets. It is suggested that cisplatin-induced, and possibly other cytotoxic drug-induced vomiting may involve a 5-HT M-receptor mechanism.
 ...
PMID:Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. 374 46

The administration to the ferret of cisplatin, 10mg/kg (i.v.), caused an intense emetic response that was prevented by ICS 205-930 (0.1 and 1.0 mg/kg i.v.) and metoclopramide (4.0 mg/kg i.v.). Smaller doses of ICS 205-930 (0.01 mg/kg i.v.) and metoclopramide (2.0 mg/kg i.v.) attenuated the emetic response to cisplatin. It is concluded that the potent action of ICS 205-930 against cisplatin-induced emesis is the consequence of a 5-hydroxytryptamine M-receptor antagonism which may also contribute to the antiemetic action of metoclopramide.
 ...
PMID:5-Hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. 377 21

Drugs interacting with serotonin (5-hydroxytryptamine, 5-HT) receptors are of value in the treatment of several gastrointestinal disturbances. Selective 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) are widely utilized to control emesis induced by chemotherapy and radiation, while agonists at 5-HT4 receptors (cisapride, renzapride, BIMU compounds) are endowed with gastrointestinal prokinetic action. Here we overview the therapeutic potential of drugs with potent mixed 5-HT4 agonist/5-HT3 antagonist properties (i.e. BIMU 1) in the management of anticancer therapy-induced emesis and of intestinal adynamic post-operative conditions associated with vomiting. In the former situation, the agonism at 5-HT4 receptors is expected to be of benefit via two possible mechanism: (i) inhibition of 5-HT release from enterochromaffin cells; (ii) restoration of anally driven peristaltic waves in the upper gastrointestinal tract. Moreover, 5-HT4 receptor-induced prokinetic activity may counteract colonic constipation, an unwanted effect which occurs in a number of patients treated with pure 5-HT3 receptor antagonists. Additionally, the above mentioned drugs might be of value in post-operative conditions associated with intestinal adynamia and emesis sensitive to 5-HT3 receptor blockade.
 ...
PMID:Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis. 747 21

Deoxynivalenol (DON) produces two characteristic toxicological effects, decreased feed consumption (anorexia) and emesis. Both effects have been linked to increased central (CNS) serotoninergic activity. Although there has also been some indication of a peripheral involvement, the role of blood pools of serotonin and related compounds in mediating DON toxicity is not well defined. In this study, the effect of DON on plasma concentrations of serotonin (5-hydroxytryptamine, 5HT), 5HIAA (5-hydroxyindoleacetic acid) and tryptophan (TRP), as a reflection of an induced peripheral serotoninergic system, was investigated in swine. Typical values for the plasma concentrations of 5HT, 5HIAA, and TRP were established in pigs. Following administration of DON, either intragastrically or intravenously, concentration changes in these substances were measured over an eight hour period. The effect of low and high toxin doses were also compared. Analyses showed no effect on plasma levels of the compounds of interest, even at sufficient toxin doses to invoke emesis in the test animals. Any variation over the course of the study remained within acceptable control limits. These results indicated no peripheral effect by DON which could account for the increased serotoninergic activity associated with altered feeding behaviour or emesis.
 ...
PMID:The effect of deoxynivalenol on serotoninergic neurotransmitter levels in pig blood. 752 34

Two randomized, double-blind placebo-controlled ondansetron dose ranging studies in patients receiving high-dose cyclophosphamide (with or without doxorubicin) were completed in the US. These studies enable the pattern of emesis and nausea for 3 days following high-dose cyclophosphamide to be described and give some insight into the mechanisms of emesis which may be operating. Nausea and vomiting induced by cyclophosphamide-based chemotherapy has a long latency of onset (8-13 h) and continues for at least 3 days. These findings are of particular importance as many of these patients receive chemotherapy as outpatients and emphasize the need for appropriate anti-emetic prophylaxis for patients at home. Ondansetron was extremely effective over this time in the control of emesis and nausea. These results suggest that high-dose cyclophosphamide-induced emesis over days 1-3 is largely mediated via 5-hydroxytryptamine (5-HT) and 5-HT3 receptors.
 ...
PMID:The pattern of emesis following high-dose cyclophosphamide and the anti-emetic efficacy of ondansetron. 754 Aug 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>