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)

Several serotonin3 (5-HT3) antagonists have been shown to attenuate the anxiogenic effects of the serotonergic agent, m-chlorophenylpiperazine (m-CPP), in animal models, but little data regarding possible effects of 5-HT3 antagonists on responses to m-CPP are available from studies in humans. Therefore, we studied the behavioral, physiological and neuroendocrine responses of 12 healthy volunteers to i.v. administered placebo and m-CPP (0.08 mg/kg), with and without i.v. pretreatment with the selective 5-HT3 antagonist, ondansetron (0.15 mg/kg). Compared to placebo, m-CPP given alone significantly increased ratings of anxiety and several other behavioral measures. m-CPP also produced statistically significant increases in temperature, systolic and diastolic blood pressure, heart rate, and in plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin and norepinephrine. Responses to ondansetron given alone were no different from those of placebo. Pretreatment with ondansetron did not affect peak behavioral responses to m-CPP, but was associated with a significantly earlier return to baseline levels of ratings of anxiety and functional deficit as well as a summary measure of overall behavioral effects. Following ondansetron pretreatment, the increases produced by m-CPP in systolic and diastolic blood pressure and heart rate were no longer significantly different from placebo. Ondansetron pretreatment significantly reduced their plasma cortisol response to m-CPP without affecting the other plasma hormone responses. Plasma concentrations of m-CPP were unaffected by ondansetron pretreatment. These findings suggest that in normal human subjects some behavioral, cardiovascular and neuroendocrine effects of m-CPP may be partially modulated by 5-HT3 receptor-mediated mechanisms.
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PMID:Behavioral, physiological and neuroendocrine responses in healthy volunteers to m-chlorophenylpiperazine (m-CPP) with and without ondansetron pretreatment. 910 5

Obsessive-compulsive disorder (OCD) has been linked to abnormal function of brain serotonin (5-HT) pathways. Since ondansetron is a highly selective 5-HT3 receptor antagonist, the present study was undertaken to investigate 5-HT3 function in OCD. We administered m-CPP (0.08 mg/kg i.v.) and the potent 5-HT3 antagonist, ondansetron (0.15 mg/kg i.v.), to 11 OCD patients. All of the subjects received four separate challenges (m-CPP + placebo, m-CPP + ondansetron, ondansetron + placebo and placebo + placebo). In comparison to placebo, administration of m-CPP was associated with significant behavioral effects, particularly self-rated measures of anxiety, altered self-reality, functional deficit and OCD symptoms. Pretreatment with ondansetron did not affect any of the self-rated behavioral symptoms. After administration of m-CPP relative to placebo, significant increases in plasma cortisol and prolactin were found. These changes were not affected by ondansetron. In conclusion, our results do not support the hypotheses that 5-HT3 receptor-mediated mechanisms modulate m-CPP's behavioral and neuroendocrine effects in patients with OCD.
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PMID:Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results. 967 22

The influence of single and multiple oral doses of ondansetron, a selective 5-HT3 receptor antagonist, was evaluated against placebo on cholecystokinin tetrapeptide (CCK-4)-induced behavioral and neuroendocrine changes in humans. As compared to placebo, subjects receiving acute ondansetron treatment showed a significant decrease in the sum intensity of CCK-4-induced-panic symptoms (iPSS). Pre-CCK-4 neuropeptide Y (NPY) plasma levels were significantly higher and maximal changes in cortisol, growth hormone, and prolactin secretion from baseline (delta max) were significantly lower in the ondansetron group. After ondansetron and placebo chronic administration, there were no statistical differences in the iPSS between groups. Pre-CCK-4 NPY plasma levels were significantly higher; whereas, delta max for NPY significantly lower in the ondansetron group as compared to placebo. These results suggest a role for the 5-HT3 receptor in the neurobiology of panic disorder through a possible interaction with CCK and NPY systems. Ondansetron chronic effect on CCK-4-induced behavioral changes needs further exploration.
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PMID:Acute and chronic role of 5-HT3 neuronal system on behavioral and neuroendocrine changes induced by intravenous cholecystokinin tetrapeptide administration in humans. 988 97

1. Central serotoninergic participation in prolactin (PRL) secretion regulation is a well-established event. Furthermore, 5-HT may participate in the mediation of stress-induced PRL release. 2. The authors investigated the effect of the blockade of 5-HT3 receptors on the PRL release induced by immobilization stress in male rats. 3. Pretreatment with the 5-HT3 receptor antagonist, ondansetron (0.10-1.0 mg/kg i.p.), inhibited about 50% of the PRL response to immobilization stress. A lower dose of ondansetron (0.05 mg/kg i.p.) had no effect on the PRL response. No dose-response inhibition was observed. 4. It is concluded that serotoninergic activation related to the mediation of the stress-induced PRL response involves the 5-HT3 receptors.
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PMID:Involvement of 5-HT3 receptors in the prolactin release induced by immobilization stress in rats. 1037 32

SSRI-induced sexual dysfunction affects 30% to 50% or more of individuals who take these drugs for depression. Biochemical mechanisms suggested as causative include increased serotonin, particularly affecting 5HT2 and 5HT3 receptors; decreased dopamine; blockade of cholinergic and alpha-1 adrenergic receptors; inhibition of nitric oxide synthetase; and elevation of prolactin levels. Five approaches to treatment include conservative approaches such as wait and see, decrease dosage, and drug holidays. More aggressive strategy for treating SSRI-induced sexual dysfunction are changing antidepressants and augmentation.
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PMID:Mechanisms and treatments of SSRI-induced sexual dysfunction. 1238 82

Abstract The interaction of galanin (GAL) with serotonin (5-HT) in the regulation of prolactin (PAL) secretion was investigated in urethaneanesthetized male rats. Intracerebroventricular administration of 5-HT (1 and 10 mu g) and GAL (1 mu g) caused an increase in plasma PRL levels, but co-administration of GAL did not show any additive effect on 5-HT-induced PRL secretion. Pretreatment with methysergide (0.25 mg/kg), a nonselective 5-HT1 and 5-HT2 receptor antagonist, partially inhibited the PRL increase induced by GAL. On the other hand, neither ketanserin (0.25 mg/kg), a selective 5-HT2 receptor antagonist, nor ICS 205-930 (0.25 mg/kg), a selective 5-HT3 receptor blocker, had any effect on GAL-induced increase in PRL secretion. Parachlorophenylalanine (300 mg/kg), a 5-HT synthesis inhibitor, however, caused a marked enhancement of PRL release induced by GAL, which was partially inhibited by a 5-HT neurotoxin, 5, 6-dihydroxytryptamine. Parachlorophenylalanine also caused a potentiation of 5-HT-induced PRL release, possibly by sensitizing 5-HT receptors. These findings suggest that 5-HT receptors are, at least partly, involved in GAL-induced PRL release in the rat.
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PMID:Galanin interacts with serotonin in stimulating prolactin secretion in the rat. 1921 Mar 86


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