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Serotonin Antagonists (serotonin + antagonist)
Selected AbstractsPersonal view: a potential novel treatment for fatigue complicating chronic liver disease , how should its efficacy be evaluated?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006E. A. JONES Summary Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease. However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue. Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated. [source] Antiepileptic Drugs in Migraine PreventionHEADACHE, Issue 2001Ninan T. Mathew MD Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including , -blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P = .09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P = .0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P = .0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention. [source] Willan's itch and other causes of pruritus in the elderlyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2005Jon R. Ward MD Itch in the elderly presents a diagnostic and therapeutic challenge. A thorough history, review of systems, and physical examination are critical to determining its cause. Examination of the skin may be misleading. There are frequently only secondary lesions, eczematous changes, lichenification, and excoriation, which may be misdiagnosed as a primary dermatitis. Xerosis may be the cause, but it is sometimes merely coincidental. If primary lesions are present, a skin biopsy can enable a diagnosis to be made. Systemic causes of itch, such as cholestasis, uremia, hyperthyroidism, medications, or lymphoma, must be considered. If the cause remains elusive, idiopathic itching of the elderly or so-called "senile pruritus" may be considered. However, we propose to discard the term "senile pruritus", which can be offensive and frightening. We propose to replace it with "Willan's itch". Robert Willan (1757,1812) is honored as one of the founders of modern dermatology thanks to his book, On Cutaneous Diseases, and its morphological approach to skin disease. He was probably the first to give a good clinical description of itching in the elderly. The diagnosis of Willan's itch should be reserved for generalized pruritus in the absence of xerosis or other recognizable cause. The pathophysiology of this form of pruritus is poorly understood, but it is likely that age-related changes of the skin, cutaneous nerves, and other parts of the nervous system play a role. Anecdotal and limited data suggest that gabapentin, cutaneous field stimulation, serotonin antagonists, and ultraviolet B phototherapy may attenuate itch in some of these patients. [source] Inhibitory effect of serotonin antagonists on JC virus propagation in a carrier culture of human neuroblastoma cellsMICROBIOLOGY AND IMMUNOLOGY, Issue 9 2009Souichi Nukuzuma ABSTRACT Human polyomavirus, JCV, causes fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). It has been shown that 5HT2AR acts as a cellular receptor for JCV on human glial cells. In the current study, we examined the inhibitory effects of 5HT2AR antagonists, ketanserin and ritanserin, both on JCV infection and on propagation by using human neuroblastoma cells IMR-32 and JCI, which continuously produce JCV. Transcriptional analysis revealed that 5HT2AR was constitutively expressed in JCI cells. Treatments with 5HT2AR antagonists led to a significant reduction in the titers of progeny viruses and the population of infected JCI cells. In addition, the amount of JCV genomic DNA was decreased in JCI cells in the presence of 5HT2AR antagonists. These results indicate that 5HT2AR antagonists have an inhibitory effect on JCV infection and reproduction, and JCI cells are applicable to an experimental model for pharmacological evaluation of antiviral agents against JCV. [source] The effect of serotonin and serotonin antagonists on bladder cancer cell proliferationBJU INTERNATIONAL, Issue 3 2006EMAD J. SIDDIQUI OBJECTIVE To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3). MATERIALS AND METHODS HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT1A, 5HT1B, 5HT1D, 5HT2, 5HT3 and 5HT4). After 72 h, cell viability was assessed using the crystal violet assay. The presence of 5HT receptor subtypes on HT1376 cells and sections of human bladder cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS 5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10,8m as compared to the control at 72 h. At 10,4m, 5HT1A antagonist (NAN-190 hydrobromide) and 5HT1B antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT1A and 5HT1B receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT1A and 5HT1B receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION 5HT1A and to a greater extent 5HT1B antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT1A and 5HT1B receptors. These results highlight the potential use of 5HT1A and 5HT1B antagonists in the treatment of bladder cancer. [source] | ||||||||||