The antiobesity action of (S)-(+)-1-(4-chlorophenylthiomethyl)-N-methylethylamine fumarate (AO-124)
| Autor: | Takao Matsuo, Kanji Meguro, Hitoshi Ikeda, Go Kito, Kozo Shimakawa |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Methysergide Hypothalamus Middle Biology chemistry.chemical_compound Dogs Internal medicine Appetite Depressants Intestine Small medicine Ethylamines Animals Obesity 5-HT receptor Pharmacology Gastric emptying Insulin Gluconeogenesis Rats Inbred Strains Glucose Tolerance Test Lipids Small intestine Rats Rats Zucker medicine.anatomical_structure Endocrinology chemistry Mechanism of action Gastric Emptying Anorectic Female medicine.symptom 2-Deoxy-D-glucose medicine.drug |
| Zdroj: | European journal of pharmacology. 125(2) |
| ISSN: | 0014-2999 |
| Popis: | The antiobesity effects of (S)-(+)-1-(4-chlorophenylthiomethyl)-N-methylethylamine fumarate (AO-124) were examined in rats and dogs. AO-124 suppressed food intake dose dependently in normal, Zucker fatty and VMH-obese rats, and beagle dogs. Its anorectic activity was not altered by pretreatment with methysergide, a serotonin receptor blocker. AO-124 also reduced the hyperphagia induced by 2-deoxy-D-glucose but not that induced by insulin, noradrenaline or muscimol, suggesting that the anoretic mechanism of AO-124 may be implicated in a glucostatic regulatory system of feeding. In addition, AO-124 decreased insulin secretion in response to an oral, but not an intravenous, glucose load. Such a suppression in insulin secretion may be explained by slow absorption of glucose from the intestine: AO-124 delayed the gastric emptying time of glucose and inhibited the active transport of glucose as observed in the everted small intestine. Two week administration of AO-124 to Zucker fatty rats resulted in a significant reduction of plasma insulin levels, body weight gain, and body lipid without exerting any changes in body protein. These findings indicate that AO-124 may be useful as an antiobesity agent on the basis of its unique mechanisms of action. |
| Databáze: | OpenAIRE |
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