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)

The emetic action of 4-(m-chlorophenylcarbamoyloxy)-2- butynyltrimethylammonium chloride (McN-A-343) was investigated in the unanaesthetized cat, after it was injected into the cerebral ventricles, through chronically-implanted cannulae. Intracerebroventricular injection of McN-A-343 produced dose-dependent and shortlasting emesis, which was not completely abolished after ablation of the area postrema. The predominantly selective muscarinic M1 antagonist, pirenzepine as well as the mixed muscarinic M1 and M2 antagonist, atropine, injected into the cerebral ventricles, attenuated or abolished the emesis evoked by intracerebroventricular McN-A-343. Both atropine and pirenzepine produced dose-dependent inhibition of the emesis evoked by McN-A-343. However, the ID50 value for atropine was approximately five times greater than that for pirenzepine. Abolition of McN-A-343-induced emesis only occurred with the largest dose of atropine (1 mg). On the other hand, selected ganglionic blocking agents, an alpha- and beta-adrenoceptor blocking agent, a dopamine antagonist, a 5-hydroxytryptamine antagonist and an antihistamine, all injected into the cerebral ventricles, had no significant effect on emesis evoked by McN-A-343, similarly injected. The emetic response to intracerebroventricular injection of McN-A-343 was attenuated or abolished in cats pretreated with hemicholinium-3, triethylcholine, reserpine and 6-hydroxydopamine, intracerebroventricularly. On the contrary, the emetic response to intracerebroventricular injection of McN-A-343 was not altered in cats pretreated with intracerebroventricular injections of bretylium, alpha-methyl-p-tyrosine and 5,6-dihydroxytryptamine. It is postulated that the emesis produced by McN-A-343, injected into the cerebral ventricles, is mediated through muscarinic M1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Emesis induced by 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343): evidence for a predominant central muscarinic M1 mediation. 246 Jul 97

1. The 5-hydroxytryptamine (5-HT3) receptor antagonist, GR 38032F, which possesses potent anti-emetic properties in vomiting induced by cancer chemotherapeutic drugs, has been tested to determine its value in the prophylaxis of motion sickness induced by cross-coupled stimulation. The double-blind trial compared GR 38032F with both a placebo (lactose) and with hyoscine. In addition, studies of ocular pursuit and saccadic eye movements were carried out following the administration of each drug. 2. The prophylactic effect of GR 38032F on motion-induced nausea was indistinguishable from that of placebo, whereas following hyoscine subjects showed a highly significant (P less than 0.001) increase in tolerance to cross-coupled stimulation. Tests of oculomotor function showed no effect on saccadic eye movement from either drug. However, both drugs produced a significant (P less than 0.05) though small reduction in eye velocity gain during pursuit eye movement. 3. These findings suggest that the 5-HT3 receptor is not involved in the neural pathways that bring about motion sickness, but that it may have a role in the control of ocular pursuit. The absence of an anti-motion sickness effect from a drug that is effective in the treatment of vomiting induced by cancer chemotherapy serves to emphasize that different neural mechanisms are involved in the generation of motion sickness.
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PMID:The effect on motion sickness and oculomotor function of GR 38032F, a 5-HT3-receptor antagonist with anti-emetic properties. 252 20

An open study of the new antiemetic BRL 43694A, a 5-hydroxytryptamine-3-receptor antagonist, was performed in 29 patients undergoing highly emetogenic cancer chemotherapy (25 patients received cisplatin in a dose greater than or equal to 50 mg/m2). Patients received BRL 43694A as a 30-minute infusion one hour after the administration of chemotherapy. 7 patients were treated with 40 micrograms/kg and 13 patients with 100 micrograms/kg BRL 43694A; the last 9 patients received an initial dose of 40 micrograms/kg with a provision for two additional interventional doses over 24 hours in the event of prolonged nausea or vomiting. 14 patients experienced no vomiting (48%) and 13 patients (45%) had 1-5 vomiting episodes over 24 hours following administration of the cytostatic agents. BRL 43694A did not cause major side effects. Based on our preliminary experience the new 5-HT3-receptor antagonist BRL 43694A is a potent antiemetic drug for the treatment of chemotherapy-induced nausea and vomiting.
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PMID:[BRL 43694A--a 5-hydroxytryptamine receptor blocker as an antiemetic in cytostatic therapy]. 254 16

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

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

In ferrets, the selective 5-hydroxytryptamine (5-HT) 5-HT3 receptor antagonist BRL 43694 given as a single injection (0.05-0.5 mg kg-1 i.v.) before cisplatin, or by divided dose (2 x 0.005-2 x 0.5 mg kg-1 i.v.) before and after cisplatin dramatically reduced or abolished the severe cisplatin-induced vomiting. BRL 43694 also substantially reduced the vomiting induced by cyclophosphamide:doxorubicin, and prevented the trimelamol-induced emesis. The severe emesis caused by whole body exposure to X-irradiation was prevented by intravenous or oral BRL 43694. A single i.v. dose of BRL 43694 given during an emetic episode or within the peak emetic period, abolished the vomiting induced by the cytotoxic drugs and by X-irradiation, usually within 30 s. Where the induction of emesis was prevented or subsequently abolished by BRL 43694, the associated behaviour (subjectively assessed as nausea) was also absent or greatly attenuated. BRL 43694 (0.1 mg kg-1 i.v.) did not affect the emesis evoked in dogs by the dopamine agonist apomorphine. The potent anti-emetic activity of BRL 43694 is discussed in terms of potential clinical use, and of the fundamental role that 5-HT3 receptors may play in the mechanisms of nausea and vomiting.
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PMID:The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694. 285 11

In unanesthetized cats the emetic action of dimethylphenylpiperazinium (DMPP) was investigated, after it was injected into the cerebral ventricles through chronically implanted cannulae. DMPP injected in 0.2-2.0 mg doses into the cerebral ventricle produced dose-dependent vomiting, which was abolished after ablation of area postrema. However, copper sulfate given intragastrically evoked vomiting in cats with an ablated area postrema. Further, the emetic response to ICV DMPP and to intragastric copper sulfate was depressed or abolished in cats pretreated with ICV reserpine. The emetic response to ICV DMPP, but not that caused by intragastric copper sulfate, was potentiated in cats pretreated with ICV 5,6-dihydroxytryptamine. Ganglionic blocking agents, mecamylamine and hexamethonium, injected ICV prevented the vomiting elicited by ICV DMPP. On the other hand, selected anti-muscarinic drugs, alpha and beta adrenergic antagonists, dopamine antagonists, antihistamines and a 5-hydroxytryptamine (5-HT) antagonist all injected into the cerebral ventricles had virtually no effect on the vomiting induced by DMPP. It is postulated that DMPP evokes vomiting by its action on nicotinic receptors of nerve cells within the area postrema but not on catecholaminergic, serotonergic, or cholinergic receptors. Finally, 5-HT and acetylcholine could also be involved in the inhibition of the complex mechanisms underlying the central regulation of vomiting.
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PMID:Dimethylphenylpiperazinium-induced vomiting: nicotinic mediation in area postrema. 286 24

The emetic action of noradrenaline was investigated in unanesthetized cats, after it was injected into the cerebral ventricles through chronically implanted cannulae. Intracerebroventricular injection of noradrenaline produced dose-dependent and shortlasting emesis, which was abolished after ablation of the area postrema. However, copper sulphate, given orally, evoked emesis in cats with an ablated area postrema. The selective alpha-2 adrenoceptor antagonist, yohimbine, as well as the mixed alpha-1 and alpha-2 adrenoceptor blocking drugs, phentolamine, tolazoline, phenoxybenzamine and dihydroergotamine, but not the selective alpha-1 adrenoceptor antagonist, prazosin, all injected into the cerebral ventricles, attenuated or blocked the emesis evoked by intracerebroventricular injection of noradrenaline. Of the alpha-adrenoceptor antagonist, only yohimbine produced dose-dependent inhibition of the emesis induced by noradrenaline. On the contrary, selected beta-adrenoceptor blocking agents, an antimuscarinic drug, a ganglionic blocking agent, an antihistamine, dopamine antagonists and a 5-hydroxytryptamine antagonist, all injected into the cerebral ventricles, had no significant effect on the emesis induced by noradrenaline, similarly injected. The emetic response to intracerebroventricular injection of noradrenaline, as well as to intragastric administration of copper sulphate was not altered in cats pretreated with intracerebroventricular injections of alpha-methyl-p-tyrosine and bretylium. On the other hand, the emetic response to intracerebroventricular injection of noradrenaline and to intragastric administration of copper sulphate was attentuated or blocked in cats pretreated with reserpine intracerebroventricularly. Moreover, in cats pretreated with intracerebroventricular injection of 6-hydroxydopamine and hemicholinium, the emesis induced by intracerebroventricular administration of noradrenaline but not that produced by intragastric injection of copper sulphate, was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Noradrenaline-induced emesis. Alpha-2 adrenoceptor mediation in the area postrema. 288 65

The intravenous injection of cisplatin in the ferret caused a consistent emetic (vomiting/retching) response. Emesis induced by cisplatin was abolished by the 5-hydroxytryptamine (5-HT) M-receptor antagonists ICS205-930, zacopride, dazopride and metoclopramide. The neuroleptic agents haloperidol, fluphenazine, domperidone, sulpiride and tiapride also antagonized emesis induced by cisplatin but only a proportion of the animals were completely protected and diazepam and prednisolone only reduced the intensity of the response. It is concluded that compounds used in the clinic to antagonise emesis induced by chemotherapy are effective in the ferret model. Antagonism of emesis induced by cisplatin in the ferret was most potently achieved by the use of the 5-HT M-receptor antagonists ICS205-930 and zacopride. However, an antagonism of dopamine receptors would appear relevant to the anti-emetic effects of the neuroleptic agents and may contribute to the anti-emetic effects of metoclopramide. Diazepam and prednisolone exert their modest antagonism by unknown mechanisms. The use of the 5-HT M-receptor antagonists is revealed as a novel approach to the treatment of emesis induced by cisplatin.
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PMID:Emesis induced by cisplatin in the ferret as a model for the detection of anti-emetic drugs. 289 Jan 17

The behavioral effects of several histamine H1 antagonists were compared in groups of squirrel monkeys trained to respond under fixed-interval schedules involving response-produced shock or termination of a stimulus associated with shock. Low to intermediate doses of the conventional H1 antagonists chlorpheniramine (up to 3.0 mg/kg), diphenhydramine (up to 1.0 or 3.0 mg/kg), pyrilamine (up to 3.0 mg/kg) and tripelennamine (up to 0.3 or 1.0 mg/kg) produced dose-related increases in response rate under all conditions in which they were studied; higher doses either increased responding less or decreased it. In contrast, a wide range of doses of the novel H1 antagonists AHR 11325 (1.0-30.0 mg/kg), astemizole (up to 10.0 mg/kg) and loratadine (up to 17.0 mg/kg) usually had little effect on responding, although decreases in response rate accompanied by emesis were observed after the highest doses in some monkeys. Other H1 antagonists including phenindamine (0.03-17.0 mg/kg), promethazine (0.03-5.6 mg/kg) and terfenadine (0.1-10.0 mg/kg) had different effects in individual subjects (i.e., dose-related increases in response rate in some monkeys and either little change or dose-related decreases in responding in other monkeys). The dopamine uptake inhibitors cocaine (0.01-1.0 mg/kg) and bupropion (0.1-10.0 mg/kg) had behavioral effects similar to those of chlorpheniramine, diphenhydramine, pyrilamine and tripelennamine, whereas the muscarinic antagonist atropine (0.03-1.0 mg/kg), the serotonin 5-hydroxytryptamine/5-hydroxytryptamine antagonist cyproheptadine (0.03-1.0 mg/kg), the norepinephrine uptake inhibitor desmethylimipramine (0.03-3.0 mg/kg) and the benzodiazepine diazepam (0.3-30.0 mg/kg) produced only dose-related decreases in response rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Behavioral effects of histamine H1 antagonists: comparison with other drugs and modification by haloperidol. 289 93


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