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5-Hydroxytryptamine (5-HT3) receptor antagonists. 1. Indazole and indolizine-3-carboxylic acid derivatives.

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Metoclopramide (1) is a gastric motility stimulant and a weak dopamine and 5-HT3 receptor antagonist. Conformational restriction of the (diethylamino)ethyl side chain of 1 in the form of the azabicyclic tropane gave 3, a very potent gastric motility stimulant and 5-HT3 receptor antagonist but devoid

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

Delta9-tetrahydrocannabivarin as a marker for the ingestion of marijuana versus Marinol: results of a clinical study.

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Delta9-tetrahydrocannabinol (THC), the main psychologically active ingredient of the cannabis plant (marijuana), has been prepared synthetically and used as the bulk active ingredient of Marinol, which was approved by the FDA for the control of nausea and vomiting in cancer patients receiving

Pharmacological properties of a novel class of 5-HT3 receptor antagonists.

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The pharmacological profile of six representative members of a novel class of 5-HT3 receptor antagonists is described. The compounds are esters and amides of benzimidazolone-1-carboxylic acid with a basic azabicycloalkyl moiety (compounds 1-3) and their respective ethyl derivatives (compounds 4-6).

5-hydroxytryptamine3 receptors in the human brain: autoradiographic visualization using [3H]ICS 205-930.

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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

Structural characterization of chromone C-glucosides in a toxic herbal remedy.

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Two novel compounds, 8-C-D-glucopyranosyl-7-hydroxy-5-methylchromone-2-carboxylic acid and a 2-O'-p-coumaroyl derivative thereof, were identified in a herbal tea that caused severe vomiting in a South African patient who had taken the traditional remedy to clean his stomach. For structural

The metabolic disposition of aprepitant, a substance P receptor antagonist, in rats and dogs.

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The absorption, metabolism, and excretion of [14C]aprepitant, a potent and selective human substance P receptor antagonist for the treatment of chemotherapy-induced nausea and vomiting, was evaluated in rats and dogs. Aprepitant was metabolized extensively and no parent drug was detected in the

Therapeutic efficacy and safety of pidotimod in the treatment of urinary tract infections in children.

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The activity of pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) was studied vs. placebo in a double-blind, randomized, multicentre trial, involving 60 pediatric patients with recurrent urinary tract infections. Recovery from acute

Hyperglycinemia and propionyl coA carboxylase deficiency and episodic severe illness without consistent ketosis.

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Propionyl CoA carboxylase deficiency was found in a 7-month-old boy who presented with attacks of vomiting, anorexia, weight loss, weakness, and hypotonia. He failed to thrive and had generalized seizures. He had propionic acidemia and hyperglycinemia; these are the manifestations of the ketotic

Acipimox Administration With Exercise Induces a Co-feedback Action of the GH, PP, and PYY on Ghrelin Associated With a Reduction of Peripheral Lipolysis in Bulimic and Healthy-Weight Czech Women: A Randomized Study.

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Objective: Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB,

[Single-dose toxicity studies of prulifloxacin (NM441) in mice, rats and dogs and the active metabolite (NM394) in rats].

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Single-dose toxicity studies of prulifloxacin, a new antibacterial agent, were conducted in mice, rats and dogs. In addition, a single-dose toxicity study of (+/-)-6-fluoro-1-methyl-4-oxo-7- (1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline- 3-carboxylic acid (NM394), an active metabolite of

Acute oral toxicity of the new quinolone antibacterial agent levofloxacin in mice, rats and monkeys.

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Acute oral toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was studied in ddy mice, SD rats and cynomolgus monkeys.

Synthesis of beta-cyclopropylalanines by photolysis of diacyl peroxides.

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[reaction: see text] Photolysis at 254 nm of neat (no solvent) unsymmetrical diacyl peroxides derived from cyclopropane carboxylic acids and l-aspartic acid generates protected beta-cyclopropylalanines in reasonable yields. Orthogonally protected 3-(trans-2-aminocyclopropyl)alanine (21), a key

Phase II evaluation of Lonidamine in patients with advanced malignancy.

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Lonidamine, a substituted indazole carboxylic acid with unique effects on cellular respiration, was studied in 27 patients with advanced malignancies. Of the 18 evaluable patients, 5 had small-cell lung cancer, 3 had non-small-cell lung cancer, 3 sarcoma, 2 breast cancer, and 5 other tumour types.

Phase II study of Lonidamine in cancer patients.

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12 patients with metastatic cancer were treated with the substituted indazole carboxylic acid Lonidamine at oral daily doses of 270 mg/m2. Toxicity, consisting mainly of myalgias, somnolence, hyperesthesia, anorexia and vomiting, generally decreased or disappeared over time despite continuing drug

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