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Effects of a 5-HT1A receptor agonist on acute and delayed cyclophosphamide-induced vomiting.

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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

In vivo efficacy in airway disease models of N-(3,5-dichloropyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281), a selective phosphodiesterase 4 inhibitor for inhaled administration.

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N-(3,5-Dichloro-pyrid-4-yl)-[1-(4-fluorobenzyl)-5-hydroxy-indole-3-yl]-glyoxylic acid amide (AWD 12-281) is a highly potent and selective phosphodiesterase 4 (PDE4) inhibitor that was designed to have a metabolic profile that was optimized for topical administration. The aim of the current study was

Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists.

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Dolasetron mesilate [(2 alpha, 6 alpha, 8 alpha, 9a beta)-octahydro-3-oxo-2,6-methano-2H-quinolizin-8-yl-1H-indole-3-c arboxylate monomethane-sulfonate], is a 5-HT3 receptor antagonist, which is in development for the treatment of chemotherapy-induced emesis. The compound is rapidly reduced by

Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs

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Alstonia scholaris (L.) R. Br., an evergreen tropical plant rich in indole alkaloids with significant physiological activity, is traditionally used to treat respiratory diseases in China. This study was conducted to establish the toxicity profile of the alkaloid extract (TA) of A. scholaris leaves

The effects of 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon.

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In the present study, the emetic effect of the anticancer drug cisplatin, and the protective effects of 5-HT3 receptor antagonists against cisplatin emesis were investigated in the pigeon. The experimental set-up involved the i.v. administration of drugs and subsequent observation of the percentage

Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view.

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Indoles constitute extensively explored heterocyclic ring systems with wide range of applications in pathophysiological conditions that is, cancer, microbial and viral infections, inflammation, depression, migraine, emesis, hypertension, etc. Presence of indole nucleus in amino acid tryptophan makes

Suppression of Cisplatin-Induced Vomiting by Cannabis sativa in Pigeons: Neurochemical Evidences.

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Cannabis sativa (CS, family Cannabinaceae) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigate CS for potential effectiveness to attenuate cisplatin-induced vomiting in healthy

New 5-HT3 (serotonin-3) receptor antagonists. I. Synthesis and structure-activity relationships of pyrido[1,2-a]indoles.

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A series of pyrido[1,2-alpha]indol-6(7-H)-ones was prepared and evaluated for 5-HT3 receptor antagonist activity. The structural requirements for the 5-HT3 receptor antagonist have been defined as an aromatic moiety, a basic nitrogen, and a linking acyl group. The (5-methylimidazol-4-yl)methyl group

Orally active indole N-oxide PDE4 inhibitors.

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This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-alpha

Relationship of serotonin-3 receptor antagonist activity to gastric emptying and motor-stimulating actions of prokinetic drugs in dogs.

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Drugs that enhance gastrointestinal motility include the benzamide drugs metoclopramide, cisapride and renzapride (BRL-24924). Because these agents also are serotonin-3 (5-HT3) receptor antagonists, which can promote gastric emptying in some species, the motor-stimulating properties of benzamide

Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3 antagonists in the pigeon.

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Vomiting may be induced by a variety of agents such as drugs, oncolytics, and provocative motion, as well as being conditioned to occur to environmental stimuli. Such emesis has recently been shown to be blocked by agonists at the 5-HT1A subtype of serotonin receptor. The antiemetic effects of

[Cases of gastroenteritis associated to Vibrio cholerae no 01 in Oran, Salta].

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Forty-one sporadic cases of non-O group 1 Vibrio cholerae gastroenteritis were detected in Orán, Salta, between February 1992 and February 1995. The frequency of isolation was 0.9% of the diarrhea cases. Out of 41 patients, 21 (51.2%) were older than 15 years and 25 (60.9%) were male. All the

Prolonged anti-emetic activity and 5-HT3-receptor antagonism by BRL 46470 in conscious ferrets.

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The anti-emetic activity of oral and intravenously-administered BRL 46470 (endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3yl)-2,3-dihydro-3,3- dimethyl-indole-1-carboxamide HCl) has been assessed in conscious ferrets. BRL 46470 (0.05-0.5 mg kg-1, p.o.) dose-dependently prevented emesis evoked over a 2 h

Safety, tolerability, and pharmacokinetics of sumatriptan suppositories following single and multiple doses in healthy volunteers.

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A suppository formulation of the 5HT1 agonist sumatriptan could prove an important therapeutic option in migraine patients who dislike or poorly tolerate injectable therapy and where oral tablet administration is unsuitable because of severe migraine-related vomiting. Two independent double-blind,

Phase I trial of the thymidylate synthase inhibitor AG331 as a 5-day continuous infusion.

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AG331 (N6-[4-(morpholinosulfonyl)benzyl]-N6-methyl-2, 6-diaminobenz-[c,d]-indole glucuronate) is a lipophilic thymidylate synthase inhibitor with activity in solid tumor models. On the basis of preclinical data supporting regimens of frequent drug administration, we performed a Phase I trial of

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