Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preclinical studies suggest that 5-HT3 antagonists modulate dopamine-mediated responses in the limbic system and may therefore have a therapeutic role in psychiatry. We have examined the effect of ondansetron, a specific 5-HT3 antagonist, on the psychological and psychomotor changes induced by amphetamine in human volunteers. Nine healthy males took part in this double-blind placebo-controlled balanced-crossover study. Each subject received one of three treatments in a randomised manner: (a) placebo/placebo; (b) placebo/amphetamine (15 mg); (c) ondansetron (4 mg)/amphetamine (15 mg). Subjects were assessed for self-ratings of hunger, mood, energy, alertness, restlessness, irritability, and asked to rate the abnormality of their overall subjective state. In addition, systolic blood pressure, and performance on psychomotor tests were repeatedly assessed. Although amphetamine did not cause any significant changes in self-rating of mood, energy, alterness, restlessness or irritability, it induced a significant increase in self-ratings for overall subjective state, and a significant decrease in self-ratings of hunger. Amphetamine also caused an increase in systolic blood pressure and a decrease in the mean time taken to complete the psychomotor tests. Pretreatment with ondansetron attenuated the effects of amphetamine on hunger and subjective state, but not on blood pressure or psychomotor performance tests. These findings suggest that in humans 5-HT3 receptor antagonists may partially modify the subjective effects of amphetamine, and are in keeping with results from animal studies that 5-HT3 receptor antagonists might affect neurotransmission within mesolimbic brain regions. However, it was not possible to exclude a pharmacokinetic interaction to explain the effects of ondansetron.
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PMID:Ondansetron, a 5-HT3 receptor antagonist, partially attenuates the effects of amphetamine: a pilot study in healthy volunteers. 138 3

The effect of the 5-HT3 receptor antagonist, ondansetron, on the decrease in hunger produced by amphetamine was assessed in nine male volunteers using a double-blind cross-over design. Amphetamine (15 mg orally) produced a significant decrease in self-ratings of hunger 2.5 h after administration. This effect was significantly attenuated by pre-treatment with ondansetron (12 mg orally over 24 h). These findings in humans are consistent with data from animal studies suggesting that ondansetron can attenuate certain catecholamins-mediated behaviours produced by amphetamine. However, explanations founded on pharmacokinetic factors cannot be presently excluded.
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PMID:Does ondansetron attenuate amphetamine-induced behaviour in human volunteers? 153 76

The present study was carried out to elucidate the effect of ondansetron, a selective 5-HT3 receptor antagonist, on amphetamine-induced changes in monoamine metabolism in major ascending dopamine (DA) neurons. Amphetamine (2 mg kg-1 s.c.) significantly decreased the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in nucleus caudatus and nucleus accumbens. Pretreatment with ondansetron (0.1 mg kg-1 and 1 mg kg-1 s.c., 15 min before amphetamine) failed to modify the effects of amphetamine. It is concluded that acute blockade of central 5-HT3 receptors by ondansetron does not prevent amphetamine-induced changes in monoamine metabolism in nigrostriatal or mesolimbic dopaminergic areas.
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PMID:5-HT3 receptor antagonist ondansetron does not alter effects of amphetamine on DA metabolism. 215 95

The effects of a 5-HT3 receptor antagonist MDL 72222 on cocaine- and amphetamine-induced increases in extracellular dopamine in the nucleus accumbens and the dorsal striatum were studied with microdialysis technique using halothane anaesthesized rats. Dopamine and its metabolites were measured by HPLC with electrochemical detection. Cocaine elevated extracellular dopamine in the nucleus accumbens and to a lesser extent in the dorsal striatum, but it did not affect dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. Pretreatment with MDL 72222 (25-100 micrograms/kg) dose-dependently attenuated cocaine-induced elevation of dopamine in both of the nuclei studied. Amphetamine elevated extracellular dopamine and reduced DOPAC and homovanillic acid equally in the nucleus accumbens and in the dorsal striatum. MDL 72222 also attenuated the amphetamine-induced elevation of extracellular dopamine concentration in both brain areas studied, but first at a dose of 100 micrograms/kg. The different potencies of the interactions of the 5-HT3 receptor antagonist with cocaine and amphetamine could be related to the different mechanisms by which these drugs primarily elevate extracellular dopamine.
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PMID:5-HT3 receptor antagonist MDL 72222 dose-dependently attenuates cocaine- and amphetamine-induced elevations of extracellular dopamine in the nucleus accumbens and the dorsal striatum. 873 67

Three kinds of neurotransmitters: histamine, acetylcholine and noradrenaline, play important roles in the neural processes of motion sickness, because antihistamines, scopolamine and amphetamine are effective in preventing motion sickness. Histamine H1-receptors are involved in the development of the symptoms and signs of motion sickness, including emesis. On provocative motion stimuli, a neural mismatch signal activates the histaminergic neuron system in the hypothalamus, and the histaminergic descending impulse stimulates H1-receptors in the emetic center of the brainstem. The histaminergic input to the emetic center through H1-receptors is independent of dopamine D2-receptors in the chemoreceptor trigger zone in the area postrema and serotonin 5HT3-receptors in the visceral afferent, which are also involved in the emetic reflex. Antihistamines block emetic H1-receptors to prevent motion sickness. Scopolamine prevents motion sickness by modifying the neural store to reduce the neural mismatch signal and by facilitating the adaptation/habituation processes. The noradrenergic neuron system in the locus coeruleus is suppressed by the neural mismatch signal. Amphetamine antagonizes mismatch-induced suppression of noradrenergic neural transmission, resulting in preventing motion sickness.
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PMID:Neural mechanisms of motion sickness. 1128 16