Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibition of deprivation-induced intake by naloxone was significantly enhanced by the 5-hydroxytryptamine3 (5-HT3) antagonist ICS-205,930. Interactions between naloxone and either the general 5-HT antagonist methysergide or the 5-HT2 antagonist ritanserin or ketanserin produced smaller effects. The present study evaluated whether 2-deoxy-D-glucose (2DG, 400 mg/kg) hyperphagia was affected by methysergide (0.5-5 mg/kg), ritanserin (0.25-2.5 mg/kg), or ICS-205,930 (0.5-5 mg/kg) alone or in combination with naltrexone (0.25 and 2.5 mg/kg). Only ICS-205,930 stimulated spontaneous intake for up to 4 h in the light cycle. Only ritanserin (1.25 mg/kg) transiently reduced 2DG hyperphagia. The dose-dependent decreases in 2DG hyperphagia by naltrexone were significantly enhanced by the dose range of ICS-205,930. The inhibition of 2DG hyperphagia by the low naltrexone dose was enhanced by methysergide (5 mg/kg) and ritanserin (1.25 mg/kg). These data suggest that the 5-HT3 receptor primarily interacts with opioid systems to modulate 2DG hyperphagia and that one possible locus of interaction is in the caudal brainstem.
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PMID:Naltrexone, serotonin receptor subtype antagonists, and glucoprivic intake: 1. 2-Deoxy-D-glucose. 151 47

Opiate antagonist inhibition of deprivation-induced intake and 2-deoxy-D-glucose (2DG) hyperphagia is significantly enhanced by the 5-hydroxytryptamine3 (5-HT3) antagonist, ICS-205,930. Interactions between opiate antagonists and either 5-HT or 5-HT2 antagonists produced smaller effects. The present study evaluated whether insulin (5 U/kg) hyperphagia was affected by methysergide (0.5-5 mg/kg), ritanserin (0.25-2.5 mg/kg), and ICS-205,930 (0.5-5 mg/kg) alone or in combination with naltrexone (2.5-10 mg/kg). Whereas ICS-205,930 stimulated insulin hyperphagia across the 6-h time course, ritanserin and, to a lesser degree, methysergide reduced insulin hyperphagia. Naltrexone marginally (19-33%) reduced insulin hyperphagia. Pairing naltrexone with either ICS-205,930 or ritanserin significantly suppressed insulin hyperphagia after 2 h. Pairing naltrexone with each of the serotonin antagonists significantly enhanced insulin hyperphagia after 4 and 6 h. These data suggest that 5-HT2 and 5-HT3 receptor subtypes interact with opioid systems to modulate insulin hyperphagia. Given that central insulin reduces food intake and body weight, the interaction between serotonergic and opioid systems may occur peripherally.
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PMID:Naltrexone, serotonin receptor subtype antagonists, and glucoprivic intake: 2. Insulin. 151 48

Functional interactions between serotonergic (5-HT) and opioid drugs have been observed with 5-HT3 receptor antagonism enhancing the inhibitory actions of naloxone and naltrexone in both food-deprived and glucoprivic rats; 5-HT2A/C receptor antagonism enhanced naltrexone's inhibition of insulin hyperphagia. The present study examined whether pretreatment with either general 5-HT (methysergide: 0.5-5 mg/kg), 5-HT2A/C (ritanserin: 0.25-2.5 mg/kg), or 5-HT3 (ICS 205930: 0.5-5 mg/kg) antagonists altered the pattern and magnitude of ad lib intake of simple (sucrose: 10%) or more complex (maltose dextrin: MD, 10%) carbohydrate solutions, or naltrexone's (0.25-2.5 mg/kg) inhibition of these forms of intake. Methysergide significantly increased the pattern and magnitude of sucrose intake at low (0.5-2.5 mg/kg) doses, and transiently delayed the pattern of MD intake at high (5 mg/kg) doses. Ritanserin significantly accelerated the pattern, but not the magnitude of sucrose intake at low (0.25-1.25 mg/kg) doses without affecting MD intake. ICS 205930 reduced the magnitude of sucrose intake at the highest (5 mg/kg) dose, and transiently reduced MD intake. Naltrexone dose dependently altered the pattern and magnitude of both sucrose and MD intake. Coadministration of ritanserin and naltrexone either eliminated or delayed the pattern of opioid antagonist inhibition of both sucrose and MD intake. Methysergide and ICS 205930 pretreatment produced minor changes in the pattern of naltrexone-induced inhibition. These data indicate that 5-HT receptor differentially modulate the pattern of carbohydrate intake, and indicate differential ingestive interactions between 5-HT and opioid antagonists under challenge and palatable conditions.
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PMID:Naltrexone, serotonin receptor subtype antagonists, and carbohydrate intake in rats. 802 91

Previous behavioural studies have shown that 5-hydroxytryptamine3 (5-HT3) receptor antagonists either block or have no effect on amphetamine-induced effects. The present experiments investigated whether or not the highly selective 5-HT3 receptor antagonist ondansetron would affect the anorectic effect of a small dose (1 mg/kg) of d-amphetamine. Nondeprived male rats were tested in two feeding paradigms: consumption of a palatable sweetened mash and ingestion of a 3% sucrose solution. Ondansetron (10-100 micrograms/kg) did not antagonize amphetamine-induced anorexia; instead, in both paradigms consumption was reduced still further when the 5-HT3 antagonist was given in conjunction with amphetamine. Ondansetron given alone had significant effects on consumption, but the direction of the effect differed according to the paradigm. Sweetened mash intake was significantly increased at 30 and 100 micrograms/kg, while sucrose ingestion was significantly reduced at 10 and 30 micrograms/kg ondansetron. It is suggested that ondansetron has two opposing effects on intake, one of which (hyperphagia) can be masked by d-amphetamine, leaving an anorectic effect that augments that of d-amphetamine.
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PMID:The selective 5-HT3 receptor antagonist, ondansetron, augments the anorectic effect of d-amphetamine in nondeprived rats. 833 20

Peripherally administered, the 5-HT2 receptor agonist, alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT), significantly suppressed the food intake of food-deprived rats. alpha-Methyl-5-HT also inhibited 2-deoxy-D-glucose-induced hyperphagia in rats. The alpha-methyl-5-HT-induced hypophagia was antagonized by the 5-HT2A receptor antagonist, ketanserin. The alpha-methyl-5-HT-induced decrease in food intake of food-deprived rats was not inhibited by prior adrenodemedullation. The peripheral 5-HT3 receptor agonist, 2-methyl-5-HT, did not affect food intake in food-deprived or 2-deoxy-D-glucose-treated rats. These results suggest that the peripheral 5-HT2A receptor may participate in the regulation of food intake and that its hypophagic effects are not associated with its adrenaline-releasing effects from the adrenal gland. Lastly, the peripheral 5-HT3 receptor did not participate in feeding control.
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PMID:Effects of peripheral 5-HT2 and 5-HT3 receptor agonists on food intake in food-deprived and 2-deoxy-D-glucose-treated rats. 898 44

Mirtazapine is a presynaptic alpha-2 antagonist that has dual action by increasing noradrenergic and serotonergic neurotransmission. The enhancement of serotonergic neurotransmission is specifically mediated via 5-HT1 receptors because mirtazapine is a postsynaptic serotonergic 5-HT2 and 5-HT3 antagonist. In addition, mirtazapine has only a weak affinity for 5-HT1 receptors and has very weak muscarinic anticholinergic and histamine (H1) antagonist properties. As a consequence of its unique pharmacodynamic properties, mirtazapine is an effective, safe and well-tolerated addition to the antidepressant armamentarium. Mirtazapine is well absorbed from the gastrointestinal tract following oral administration, and it is extensively metabolized in the liver to four metabolites via demethylation and hydroxylation, followed by glucuronide conjugation. The unconjugated desmethyl metabolite is pharmacologically less active than the parent compound. Mirtazapine lacks auto-induction of hepatic isoenzymes. Although mirtazapine is a substrate of P450 isoenzymes 1A2, 2D6 and 3A4, in vitro studies show that it is not a potent inhibitor or inducer of any of these enzymes. Mirtazapine has been evaluated in a worldwide clinical development program involving approximately 4500 patients. Controlled clinical trials involving almost 2800 mirtazapine-treated patients have demonstrated the compound to be effective for the treatment of moderate-to-serve major depression. Mirtazapine was consistently superior to placebo, and equivalent in efficacy to the tricyclic antidepressants amitriptyline, doxepin and clomipramine, but with an improved tolerability profile. Mirtazapine has shown a rapid onset of action in patients with predominantly severe depressive illness in a comparative study against fluoxetine. Mirtazapine has a unique tolerability profile, since the specific postsynaptic 5-HT2 and 5-HT3 receptor blockade of mirtazapine provides early antidepressant effects without causing unwanted serotonin-related side-effects. Transient somnolence, hyperphagia and weight gain are the most commonly reported adverse events, which may be attributed to the antihistaminic (H1) activity of mirtazapine at low doses. Somnolence, the most commonly reported side-effect, appears to be less frequent at higher dosages. Mirtazapine also demonstrates important anxiolytic and sleep-improving effects, which may be related to its pharmacodynamic properties. In addition, mirtazapine does not appear to be associated with sexual dysfunction. Mirtazapine has shown no significant cardiovascular adverse effects at multiples of 7 to 22 times the maximum recommended dose. Mirtazapine is a unique addition to the antidepressant armamentarium as first-line therapy in patients with major depression and symptoms of anxiety/agitation or anxiety/somatization or complaints of insomnia and as a useful alternative in depressed patients who do not adequately respond to or are intolerant of tricyclic antidepressants or serotonin-specific reuptake inhibitors.
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PMID:Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. 1033 82