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

1. Our aim was to determine whether the cardiovascular neurones in the rostro-ventrolateral medulla (CV-RVLM neurones) were involved in the sympathoexcitation induced by stimulation of 5-HT3 receptors in the region of the nucleus tractus solitarii (NTS). Experiments were performed in pentobarbitone-anaesthetized rats, artificially ventilated and paralysed with pancuronium bromide. 2. Using extracellular recordings, different types of RVLM neurones were characterized: cardiovascular (CV), ventilation-related and baroreflex-insensitive (unidentified) neurones. The CV-RVLM cells were further subdivided into three populations according to their axonal conduction velocities: A (1.2 +/- 0.1 m s-1), B (2.5 +/- 0.2 m s-1) and C (6.8 +/- 1.1 m s-1). 3. Only the CV-RVLM neurones of the A and B categories were partially inhibited (-30 %) by a hypotensive dose (2.5 microg kg-1 i.v.) of clonidine. 4. Microinjections into the region of the commissural NTS of 1-(m-chlorophenyl)-biguanide (CPBG, 2 nmol), a selective 5-HT3 receptor agonist, elicited an increase in both lumbar sympathetic nerve discharge (SND) and arterial pressure. In addition, this treatment produced a marked excitation of CV-RVLM neurones of the A and B categories, without affecting those of the C type, as well as ventilation-related and unidentified RVLM cells. 5. The activity of the CV neurones in the caudo-ventrolateral part of the medulla oblongata (CV-CVLM) was not modified by 5-HT3 receptor stimulation in the NTS. 6. Prior intra-NTS microinjections of ondansetron (300 pmol, a selective 5-HT3 receptor antagonist) into the region of the commissural NTS prevented the excitation of A and B CV-RVLM neurones induced by CPBG. 7. Intracarotid administration of saline saturated with CO2 (chemoreceptor activation) elicited both an increase in the SND and an excitation of the clonidine-insensitive CV-RVLM neurones of the C type, without affecting A and B neurones. 8. In conclusion, the sympathoexcitation elicited following 5-HT3 receptor stimulation in the region of the commissural NTS of pentobarbitone-anaesthetized rats seems to result from the excitation of two different pools of clonidine-sensitive CV-RVLM neurones. These neurones are apparently not involved in the sympathetic component of the chemoreceptor reflex.
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PMID:Dorsal medullary 5-HT3 receptors and sympathetic premotor neurones in the rat. 951 30

Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor-inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)A receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several 'motilinomimetics' have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These 'enterokinetic' compounds are useful for treating constipation-predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.
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PMID:Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. 1020 10

Palonosetron hydrochloride is a longer-acting selective 5-HT3 receptor antagonist that has been approved for the prevention of chemotherapy-induced nausea and vomiting and is being evaluated for the prevention of postoperative nausea and vomiting. The objective of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 50 mcg/mL when mixed with any of the neuromuscular blocking drugs cisatracurium besylate 0.5 mg/mL, rocuronium bromide 1 mg/mL, succinylcholine chloride 2 mg/mL, and vecuronium bromide 1 mg/mL during simulated Y-site administration. Triplicate samples of palonosetron hydrochloride with each of the neuromuscular blocking drugs were tested. Samples were stored and evaluated for up to 4 hours at room temperature. Physical stability was assessed by turbidimetric and particulate measurements and visual inspection. Chemical stability was assessed by high-performnace liquid chromatography. All of the admixtures were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in all of the samples tested. Palonosetron hydrochloride is physically and chemically stable with cisatracurium besylate, rocuronium bromide, succinylcholine chloride, or vecuronium bromide at the concentrations tested during simulated Y-site administration over 4 hours at ambient room temperature.
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PMID:Compatibility and stability of palonosetron hydrochloride with four neruomuscular blocking agents during simulated y-site administration. 2396 8

Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly.
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PMID:Pharmacologic Agents for Chronic Diarrhea. 2657 35