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)

RU 24969 was administered s.c. to cats and found to elicit emesis with a maximally effective dose of 1.0 mg/kg. 5-Methoxytryptamine was found to have lower efficacy and to produce a higher incidence of non-specific effects while trifluoromethylphenylpiperizine (TFMPP) was devoid of emetic effects. The emesis elicited by 1.0 mg/kg of RU 24969 was not altered by pretreatment with phentolamine, haloperidol, yohimbine or (-)-propranolol, indicating that catecholamines played no role in this response. The emesis was prevented by metergoline and methysergide but not by ketanserin, cyproheptadine, mesulergine, ICS 205,930, methiothepin, trimethobenzamide or BMY 7378. An indirect argument is presented that implicates a role for 5-HT1D sites. This conclusion must remain tentative until drugs selective for this site are synthesized and tested. The emesis was also prevented by 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT), confirming that this drug has a general antiemetic effect in cats.
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PMID:RU 24969-induced emesis in the cat: 5-HT1 sites other than 5-HT1A, 5-HT1B or 5-HT1C implicated. 214 95

These results thus indicate, that ICS 205-930 is a very effective antiemetic for cancer chemotherapy-induced emesis in man. Given as a single dose prior to the chemotherapeutic agent, ICS 205-930 inhibits emesis and nausea for at least 24 hr. Together with the lack of extrapyramidal side-effects, these properties of ICS 205-930 indicate a clear superiority to the current therapeutic standard metoclopramide.
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PMID:Antiemetic action of 5-HT3 receptor antagonists: review of preclinical and clinical results with ICS 205-930. 227 46

The results of an open study designed to evaluate the prevention of cisplatin-induced emesis by the specific 5-HT3 receptor antagonist ICS 205-930 are reported. Fifty-four cancer patients, treated with diverse chemotherapy regimens, all including cisplatin (greater than = 50 mg/m2), received ICS 205-930 for a total of 165 courses. ICS 205-930 (10 mg) was given i.v. immediately before the cisplatin infusion and a second 10-mg dose was given immediately after. In 109 courses (66%) the patients did not have any vomiting episodes. Nausea was absent in 44.8% of courses. More than 3 vomiting episodes occurred only in 17 (10.4%) courses, and severe nausea only in 11 (6.6%). ICS 205-930 was extremely well tolerated. Mild headache occurred during 7 courses (4.2%) in 4 patients, hypotension during 5 courses (3%) in 3 patients and lipothymia in 2 courses (1.2%) in 2 patients. These results suggest that ICS 205-930 is an effective and well tolerated antiemetic drug in patients receiving cisplatin chemotherapy.
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PMID:Prevention of nausea and vomiting in cisplatin-treated patients by a selective 5-hydroxytryptamine (5-HT3) receptor antagonist, ICS 205-930. 228 99

The present studies demonstrate the presence of specific [3H]GR65630 binding sites within the human brainstem using the techniques of in vitro receptor autoradiography and ligand binding to homogenates. Autoradiography revealed the greatest accumulation of specific binding in the area postrema and subpostrema (AP/ASP). A lower level of specific binding was identified in the nucleus tractus solitarius (excluding area subpostrema). No specific binding was evident in the remainder of the hindbrain at this level. Discrete dissection followed by ligand binding to homogenates revealed that the specific binding of [3H]GR65630 (defined by the presence of 30 microM metoclopramide) was differentially distributed with highest levels in the AP/ASP (112.1 fmol/mg protein) and lower levels in the dorsal vagal complex (nucleus tractus solitarius--excluding the area subpostrema--dorsal motor nucleus of the vagus and hypoglossal nucleus) (DVC) and olivary nucleus (ON) (22.9 and 3.9 fmol/mg, respectively). No specific binding was detectable in the reticular formation (RF) located ventral to the dorsal vagal complex. The specific [3H]GR65630 binding site was pharmacologically similar to the 5-HT3 receptor since the potent and selective 5-HT3 receptor antagonists ICS 205-930 and zacopride (100 nM) and the agonist 5-HT (10 microM) inhibited binding to the same extent as metoclopramide in each of the individual areas (90, 60 and 20% in the AP/ASP, DVC and ON, respectively). The 5-HT1-like and 5-HT2 receptor antagonist methysergide (10 microM) failed to compete for the binding site. 5-HT3 receptor recognition sites within the AP/ASP and the DVC may be functionally involved in the ability of 5-HT3 receptor antagonists to control emesis.
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PMID:Identification and distribution of 5-HT3 recognition sites within the human brainstem. 233 96

The well-documented 5-HT3 receptor antagonists, ICS 205-930 and GR38032F, have been compared with regard to their inhibitory activity at 5-HT3 receptors to another gastrokinetic agent, zacopride. Zacopride and ICS 205-930 showed similar affinity (-log kB approximately 8.0), whereas GR38032F showed lower affinity (-log ka approximately 7.0) at 5-HT3 receptors in the guinea pig ileum. After i.v. administration to anesthetized rats, zacopride was approximately 10-fold more potent than either ICS 205-930 or GR38032F, which were equipotent as inhibitors of serotonin-induced bradycardia (5-HT3-mediated activation of the von Bezold Jarisch reflex). After oral administration to anesthetized rats, zacopride remained approximately 10-fold more potent than ICS 205-903, which was approximately 2-fold more potent than GR38032F as an inhibitor of serotonin-induced bradycardia. Furthermore, the inhibitory effectiveness of GR38032F persisted for less than 3 hr after oral administration and for less than 15 min after intravenous administration. ICS 205-930 produced maximal inhibition of serotonin-induced bradycardia for over 3 hr with heart rate returning to control values 6 hr after oral administration. Zacopride possessed the longest duration of inhibitory effectiveness in urethane-anesthetized rats with maximal inhibition still apparent 6 hr after oral administration. All three agents inhibited cisplatin-induced emesis after i.v. administration in dogs with zacopride being 10-fold more potent than ICS 205-930 or GR38032F, which were equipotent. These comparative data with three 5-HT3 receptor antagonists indicate that in animals, zacopride was more potent and longer acting than either ICS 205-930 or GR38032F. Furthermore, after oral administration to rats, GR38032F was slightly less potent than ICS 205-930 and possessed the shortest duration of action.
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PMID:Comparison of the 5-HT3 receptor antagonist properties of ICS 205-930, GR38032F and zacopride. 252 13

1. The current classification of receptors for 5-hydroxytryptamine (5-HT) is based on functional studies, and encompasses three main receptor types. 2. 5-HT1-like receptors mediate inhibition of release of various neurotransmitters from central and peripheral sites, smooth muscle contraction and relaxation (and release of endothelium-derived relaxing factor), tachycardia, a variety of behavioural actions (for example, forepaw treading, hypothermia, hyperphagia, drug discriminative stimulus properties, nociceptive pathway modulation, and anxiolytic, anti-aggressive and prosexual effects), and central neuronal excitatory and inhibitory activity. Selective antagonists for this receptor are not yet available, but the 5-HT2 receptor antagonists methysergide and methiothepin have appreciable affinity for 5-HT1-like receptors, and 5-carboxamidotryptamine is a selective agonist. 3. 5-HT2 receptors mediate smooth muscle contraction, platelet aggregation, increased capillary permeability, some behavioural syndromes (for example, head twitch and wet-dog shakes) and drug discriminative stimulus properties, central neuroexcitatory effects, and some neuroendocrine functions. Ketanserin and cyproheptadine are selective antagonists. 4. 5-HT3 receptors mediate peripheral afferent and efferent neuroexcitatory actions, anxiogenic effects, and modulation of cytotoxic drug-induced emesis, gastric emptying, and dopamine-related mesolimbic hyperactivity. Selective antagonists include cocaine, MDL 72222 and ICS 205-930; 2-methyl-5-HT is a selective agonist.
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PMID:The classification of 5-hydroxytryptamine receptors. 267 Mar 59

5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.
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PMID:Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat. 273 31

The distribution of 5-hydroxytryptamine receptors of the 5-hydroxytryptamine3 type was examined in human brain post mortem tissue, using quantitative in vitro autoradiography. The selective and potent 5-hydroxytryptamine3 receptor antagonist [3H]ICS 205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester] was used as ligand. Highest levels of labelling were found in discrete nuclei of the lower brainstem. At all levels of the spinal cord the substantia gelatinosa was also densely labelled. In contrast, specific binding in the forebrain was very low and concentrated in some regions of the limbic system. The enrichment of [3H]ICS 205-930 binding sites in nuclei of the dorsal medulla and spinal cord is in good agreement with the proposed role for 5-hydroxytryptamine in sensory processing. High densities of 5-hydroxytryptamine3 binding sites in the area postrema support a central site of action for 5-hydroxytryptamine in emesis. Finally, the presence of [3H]ICS 205-930 binding sites in the limbic system provides an anatomical substrate for the behavioural effects of 5-hydroxytryptamine3 receptor antagonists.
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PMID:5-hydroxytryptamine3 receptors in the human brain: autoradiographic visualization using [3H]ICS 205-930. 279 43

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.
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PMID:5-Hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. 377 21

The involvement of visceral afferent fibers and 5-HT3 or 5-HT4 receptors in the vomiting induced by oral administration of copper sulfate was investigated in beagle dogs. Vomiting induced by copper sulfate (100 mg/kg) was inhibited markedly by bilateral abdominal vagotomy and bilateral greater splanchnic nerve section. The vomiting induced by copper sulfate was inhibited by blocking 5-HT4 receptors with high doses (1 and 3 mg/kg, i.v.) of ICS 205-930. On the other hand, blocking 5-HT3 receptors with MDL 72222 (0.5 and 5 mg/kg, i.v.) or low doses (0.01 mg/kg i.v.) of ICS 205-930 had no apparent effect on the vomiting induced by copper sulfate. Oral administration of a 5-HT4 receptor agonist, 5-methoxytryptamine (5-MT), caused vomiting at a dose of 100 mg/kg, and the vomiting was inhibited markedly by abdominal visceral nerve section or a high dose (1 mg/kg, i.v.), but not a low dose (0.01 mg/kg, i.v.), of ICS 205-930. Intravenous administration of 5-MT (10 mg/kg) failed to induce vomiting. These results suggest that the abdominal visceral afferent fibers and possibly peripheral 5-HT4 receptors play an important role in the vomiting induced by oral administration of copper sulfate in dogs.
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PMID:Possible involvement of peripheral 5-HT4 receptors in copper sulfate-induced vomiting in dogs. 808 6


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