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Mirja Hämäläinen - One of the best experts on this subject based on the ideXlab platform.
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Oral sumatriptan for the acute treatment of migraine in children and adolescents: yet another failed study.
Cephalalgia, 2013Co-Authors: Mirja HämäläinenAbstract:Sumatriptan, a Serotonin-1 Receptor agonist specially developed for migraine, became available as a licensed product for adults more than 20 years ago. Since then, numerous controlled studies with sumatriptan have been carried out and it is widely used in adults. However, the story has not been as successful in children and adolescents as in adults. Of the few studies performed, most have shown a high placebo response rate (1–4). High placebo response has been found also in other triptan studies in children (1–4). It may be due to several factors, such as study design and shorter duration of migraine attacks in young patients (1–4). Shorter duration means a strong tendency to spontaneous recovery, which is found in placebo-treated acute attacks. Two controlled clinical studies have been reported to show efficacy against placebo with sumatriptan nasal spray (5,6), which is licensed for the treatment of migraine in children aged 12 years or older in the European Union (EU), Australia and New Zealand, but not in the United States and Canada. Only a few clinical studies have evaluated sumatriptan tablets in children and adolescents. In one of the studies, both the response to sumatriptan and to placebo was low and not statistically different (7). In one study with sumatriptan and naproxen sodium combination tablets, the pain-free response rate to the active combination was statistically significantly higher than to placebo (8). In other sumatriptan studies, the response rates both to sumatriptan and to placebo have been similarly high as in other studies with triptan tablets. Sumatriptan tablets have not yet been licensed for the treatment of migraine in children and adolescents. A group of Japanese investigators bring their contribution to a small series of pediatric sumatriptan studies (9). They report results of a double blind, placebo-controlled, 17-center, parallel-group study in adolescents, who treated one acute migraine attack either with a 25mg sumatriptan tablet or with a 50 mg sumatriptan tablet or with placebo. They enrolled 178 patients, of whom 144 patients completed the study and were included in the analysis. As the primary endpoint (i.e. pain relief) was considered at two hours postdose, the percentage was higher for placebo than for the active drug (38.6% vs 31.1%). The same endpoint at four hours post-dose was reported more often after sumatriptan (63.5%) than after placebo (51.4%), but the difference failed to achieve statistical significance (p1⁄4 0.142). The authors conclude that sumatriptan did not show statistically significant pain relief at two hours post-dose as compared to placebo. Both doses of sumatriptan tablets were well tolerated. The pain relief measures that Japanese investigators chose as primary endpoint were clinically useful, even if the best two-hour primary endpoint according to the International Headache Society (IHS) recommendations is pain freedom (10). In almost all earlier triptan trials, the lowest response rates have been approximately 49% of the active drug. Japanese response rates to both placebo and sumatriptan are lower. It is hard to say why. But one could speculate that it may be because of the patients selected for the study—either their migraine characteristics or perhaps even their ethnic pharmacogenetic specificity. Future studies could include also crossover designs (to reduce the number of patients needed and placebo effect (3,10)) with clinically meaningful endpoints (such as complete pain relief, time to onset of relief and time to meaningful relief of symptoms (11)). Clinical efficacy of sumatriptan and other triptans in children and adolescents with migraine still needs to be reported in controlled trials.
Tl Schwenk - One of the best experts on this subject based on the ideXlab platform.
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Association Between Sumatriptan Use and Ischemic Colitis
NEJM Journal Watch, 1998Co-Authors: Tl SchwenkAbstract:Sumatriptan and other Serotonin-1 Receptor agonists used in the treatment of migraine headache have been associated with myocardial ischemia and
C. Sudandiradoss - One of the best experts on this subject based on the ideXlab platform.
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The function and structural influence of selective relaxed constraint at functional intracellular loop3 of 5-HT1A Serotonin-1 Receptor family
Gene, 2012Co-Authors: J. Febin Prabhu Dass, C. SudandiradossAbstract:Serotonin (5-HT) and its Receptors have been involved in critical signal transduction mechanism and deregulation implicated in mood-related disorders. 5-HT activities are mediated through a family of transmembrane spanning Serotonin Receptors. Both within the family and species, 5-HT Receptor protein sequence diversity and 7-transmembrane structural homogeneity have long been intriguing. In this study, we have analyzed the codon site constraint in 5-HT1 subclass Receptors from 13 orthologous mammalian mRNA coding sequence. Further, the study was extended to computationally investigate the impact of non-synonymous sites with respect to function and structural significance through sequence homology algorithm and molecular dynamics simulation (MDS). Codon sites with significant posterior probability were observed in 5-HT(1A), 5-HT(1B) and 5-HT(1D) Receptor indicating variations in site constraint within the 5-HT1 sub-class genes. In 5-HT(1A) Receptor, seven sites were detected at the functional intracellular loop(3) (ICL(3)) with higher substitution rate through Codeml program. Sequence homology algorithm identifies that these sites were functionally tolerant within the mammals representing a selectively relaxed constraint at this domain. On the other hand, the root mean square deviation (rmsd) values from MDS suggest differences in structural conformation of ICL(3) models among the species. Specifically, the human ICL(3) model fluctuation was comparatively more stable than other species. Hence, we argue that these sites may have varying influence in G-proteins coupling and activation of effectors systems through downstream interacting accessory proteins of cell among the species. However, further experimental studies are required to elucidate the precise role and the seeming difference of these sites in 5-HT Receptors between species.
Said Naili - One of the best experts on this subject based on the ideXlab platform.
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Changes in exploratory activity following stimulation of hippocampal 5‐HT1A and 5‐HT1B Receptors in the rat
Hippocampus, 1995Co-Authors: Marie-christine Buhot, Said NailiAbstract:The object exploration task allows the measure of changes in locomotor and exploratory activities, habituation, and reaction to a spatial change and to novelty. The effects of intrahippocampal (dorsal CA1 field) microinjections of Serotonin 1 Receptor (5-HT1) agonists on these behavioral components were evaluated in the rat. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 5 micrograms/microliters) was used as a 5-HT1A agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93,129,16 micrograms/microliters) as a 5-HT1B agonist, and scopolamine (10 micrograms/microliters) as a muscarinic cholinergic antagonist. Scopolamine induced a long-lasting increase in locomotor activity and a lack of reaction to spatial change; both these results are in agreement with the known crucial influence of the septo-hippocampal cholinergic system in hippocampal functioning. Stimulation of 5-HT1A and 5-HT1B Receptors induced a decrease in object exploration and habituation without affecting the retrieval of spatial information. But stimulation of hippocampal 5-HT1B Receptors induced a selective change in the animal's emotional state, i.e., an initial decrease in locomotor activity and a neophobic reaction in response to a new object; such effects did not occur following stimulation of 5HT1A Receptors. These results have to be considered in the light of the anxiogenic property of 5-HT1B agonists. On the whole, they support the hypothesis of the involvement of the serotonergic system, via 5HT1A and 5-HT1B Receptors, in the modulation of hippocampal functions.
Jia-sheng Chen - One of the best experts on this subject based on the ideXlab platform.
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Effect of 5-Serotonin 1 Receptor agonists on acetic acid stimulated micturition in chronic spinal cord injury cats
Chinese journal of experimental surgery, 2012Co-Authors: Jia-sheng ChenAbstract:Objective To evaluate the effects of 5-Serotonin 1 (5-HT1) Receptor agonists on acetic acid stimulated micturition in cats with chronic spinal cord injury (SCI).Methods Chloralose-anesthetized SCI cats were catheterized through the bladder dome for filling cystometry during 0.5％ acetic acid infusion.Dose-response curves for ( R)-8-OH-DPAT (0.30-30.00 μg/kg,i.v.) or GR 46611 (0.03-300.00 μg/kg,i.v.) were followed by 5-HT1A antagonist WAY-100635 (300.00 μg/kg).Threshold volume,bladder capacity,residual volume,micturition volume,and arterial pressure were measured and the external urethral sphincter electromyogram (EUS-EMG) was recorded.Results Acid-infused SCI cats responded to (R)-8-OH-DPAT but not GR-46611 with dose-dependent increases in threshold volume,capacity,and residual volume,significantly at the dose above 10 μg/kg.Effects of (R)-8-OH-DPAT were largely reversed by WAY 100635.Neither (R)-8-OH-DPAT nor GR-46611 augmented EUS-EMG activity.Conclusion Because 5-HT1A Receptor agonists increase bladder capacity under either saline or acid infused conditions,they are promising candidates for reducing bladder hyperactivity and increasing bladder capacity in patients with chronic SCI. Key words: Spinal cord injury; Micturition; 5-Serotonin Receptor; Cat
