The Efficacy of Different Triptans for the Treatment of Acute Headache in Pediatric Migraine: A Systematic Review

Background: Serotonin receptors 5-HT1B and 5-HT1D in the cerebral arteries are activated by the 5-hydroxytryptophan agonists (triptans) to relieve the discomfort associated with migraines. Even though triptans are often used to treat acute migraines, there is some debate over their effectiveness. Objective: Our systematic review aimed to evaluate the effectiveness of triptans for acute treatment of migraine in young individuals. Methods: Utilizing the databases of Google Scholar, Cochrane Library, and PubMed, a literature search was conducted, and all papers published till July 2022 were included. This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. In addition to the Boolean operators AND, OR, and NOT, the following descriptive terms were also used: “Triptans,” “Pediatric Migraine,” “Migraine disorders,” “Headache,” “Children,” and “Adolescent.” Results: A total of 1047 studies were identified, and 25 articles were finally included in the study. 17 of them were RCTs while the remaining were non-randomized trials. Most studies recruited participants aged between 12-17 years. Among 25 studies, 7 reported sumatriptan use, 3 assessed a combination of sumatriptan and naproxen, 4 were on almotriptan, 1 on eletriptan, 6 on rizatriptan, and 4 on zolmitriptan use. Conclusion: We found that rizatriptan (good tolerability profile with a dose of 5 mg) and sumatriptan (nasal spray, 10 mg and 20 mg) had higher efficiency as compared to other triptans. Regardless of type or dose, all triptans are generally well tolerated by patients, but a few adverse effects such as light-headedness (sumatriptan), nasopharyngitis, and, muscular spasms (sumatriptan/ naproxen), somnolence, and dry mouth (rizatriptan), and dizziness (zolmitriptan group) were reported with the triptans.

Reporte de un caso de tratamiento de gastroparesia pediátrica con prucaloprida: una terapia novedosa / A case report of prucalopride treatment in pediatric gastroparesis: a novel therapy

La prucaloprida acelera el vaciamiento gástrico en adultos con gastroparesia. No existen estudios con este medicamento en niños con gastroparesia. Se presenta un niño de 8 años que consultó por síntomas posprandiales de un mes de duración, con diagnóstico de gastroparesia por gammagrafía de vaciamiento gástrico. No mejoró con metoclopramida, domperidona, eritromicina y esomeprazol. Recibió prucaloprida durante dos períodos (durante 178 y 376 días) a dosis de 0,03-0,04 mg/kg/día. Presentó mejoría en el seguimiento con el índice cardinal de síntomas de gastroparesia y gammagrafías de vaciamiento gástrico. Por la buena respuesta, la prucaloprida podría ser una opción terapéutica en la gastroparesia pediátrica.

Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy is presented who consulted for a month of postprandial symptoms, with a diagnosis of gastroparesis by gastric emptying scintigraphy. He did not improve with metoclopramide, domperidone, erythromycin, and esomeprazole. He received prucalopride for two periods (for 178 and 376 days) at doses: 0.03 - 0.04 mg/kg/day, presenting improvement in the follow-up with the cardinal gastroparesis symptom index and gastric emptying scintigraphy. Due to the good response, prucalopride may be a therapeutic option in pediatric gastroparesis.

Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats / A serotonina endógena e exógena, mas não o sumatriptano, melhora as convulsões e a neuroinflamação no modelo de convulsão induzida por pentilenotetrazol em ratos

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

RESUMO Antecedentes: A epilepsia apresenta comorbidades neuropsiquiátricas como depressão, transtorno bipolar e ansiedade. Os medicamentos que visam o tratamento da epilepsia podem ser úteis para a epilepsia e suas comorbidades neuropsiquiátricas. Objetivo: Investigar os efeitos da modulação serotonérgica em citocinas pró-inflamatórias e as convulsões no modelo de convulsão induzida por pentilenotetrazol (PTZ) em ratos. Métodos: Ratos Wistar machos foram injetados intraperitonealmente com serotonina, inibidor seletivo da recaptação da serotonina fluoxetina, sumatriptano agonista do receptor 5-HT1B / D ou solução salina 30 min antes do tratamento com PTZ. As crises comportamentais foram avaliadas pela escala de Racine. As concentrações de IL-1β, IL-6 e TNF-α no soro e tecido cerebral foram determinadas por ELISA. Resultados: A serotonina e a fluoxetina, mas não o sumatriptano, aliviaram as convulsões induzidas por PTZ ao prolongar os tempos de início das convulsões mioclônicas e tônico-clônicas generalizadas. O efeito anticonvulsivo da fluoxetina foi maior do que o da serotonina. Da mesma forma, a serotonina e a fluoxetina, mas não o sumatriptano, reduziram os aumentos induzidos por PTZ nos níveis de IL-1β e IL-6 no soro e no tecido cerebral. Nenhum dos medicamentos administrados, incluindo PTZ, alterou as concentrações de TNF-α. Conclusões: Nossos achados sugerem que a serotonina endógena e exógena exibe efeitos anticonvulsivantes por suprimir a neuroinflamação. Aparentemente, os receptores 5-HT1B / D não medeiam os efeitos anticonvulsivantes e anti-neuroinflamatórios da serotonina.

Role of 5-HT 1A and 5-HT 3 receptors in sevoflurane-induced cerebral neurotoxicity in aged rats / 中华麻醉学杂志

Objective:To preliminarily investigate the relationship between the mechanism of sevoflurane-induced cerebral neurotoxicity and receptors of 5-HT 1A and 5-HT 3 in aged rats. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 18-20 months, weighing 600-750 g, were divided into 3 groups ( n=8 each) using a random number table method: group C, group LS and group HS.In group C, group LS and group HS, 50% O 2, 1.5% sevoflurane plus 50% O 2 and 3% sevoflurane plus 50% O 2 were inhaled for 2 h, respectively.Open field test was performed at 1 day before inhalation of sevoflurane and at 1 day after the end of inhalation, the time spent in the central square, the number of crossing the grid and the number of standing on the back legs were recorded.The Morris water maze test was performed at 6 days before inhalation of sevoflurane and at 1 day after the end of inhalation, the escape latency, the total swimming distance and the number of crossing the platform were recorded.Immediately after the end of behavioral testing, the hippocampal tissues were obtained for determination of 5-HT 1A and 5-HT 3 receptors mRNA expression and the number of positive cells (using real-time reverse transcription-polymerase chain reaction assay and immunohistochemical method). Results:Compared with group C, the time spent in the central square was significantly prolonged, the number of crossing the grid and the number of standing on the back legs were decreased, the escape latency was prolonged, the total swimming distance was increased, the number of crossing platform was decreased, the mRNA expression of 5-HT 1A and 5-HT 3 was down-regulated, and the number of positive cells was decreased in HS group ( P<0.05). Conclusion:The mechanism of cerebral neurotoxicity induced by sevoflurane may be related to the down-regulation of the activities of 5-HT 1A and 5-HT 3 receptors in aged rats.

Effect of Tongxie Yaofang with or Without Saposhnikoviae Radix on Water Metabolism and 5-HT Pathway in Irritable Bowel Syndrome Rats / 中国实验方剂学杂志

Objective:To investigate the effect of Saposhnikoviae Radix on Tongxie Yaofang in regulating water metabolism and 5-serotonin（5-HT） signal system in diarrhea type irritable bowel syndrome（IBS-D）rats. Method:The 40 IBS-D SD rats were randomly divided into model group, Tongxie Yaofang wituout Saposhnikoviae Radix group (26 g·kg-1), Tongxie Yaofang decoction group (30 g·kg-1), Tongxie Yaofang with double Saposhnikoviae Radix group (34 g·kg-1),another 10 normal SD rats were selected as the normal group.Except for normal group, the rats in other groups were separated from their mothers and induced by acetic acid to establish D-IBS model. These rats in the each group were administered with corresponding drugs for 14 days. The diarrhea indexs and the water contents of the feces were observed and calculated. The Na+-K+-ATPase activities in the intestinal mucosa were detected by micro method. The contents of 5-HT were detected by enzyme linked immunosorbent assay (ELISA). The activities of monoamine oxidase A (MAO-A) were detected by chemiluminescence method. The expressions of aquaporin 4 (AQP4) in colon were detected by immunohistochemistry. Protein expression levels of HT receptor 3 (5-HT3R), HT receptor 4 (5-HT4R) and serotonin transporter (SERT) in hypothalamus and colon were detected by Western blot. Result:Compared with normal group, the fecal water contents, contents of 5-HT in hypothalamus and colon, activities of MAO-A, expressions of 5-HT3R were significantly increased in model group (P<0.01), and the activities of Na+-K+-ATPase, expressions of AQP4, 5-HT4R and SERT were reduced significantly (P<0.01). Compared with model group, the diarrhea indexs and fecal water contents, contents of 5-HT in hypothalamus and colon, activities of MAO-A, expressions of 5-HT3R were significantly decreased in each experimental group, and the activities of Na+-K+-ATPase, expressions of AQP4,5-HT4R and SERT were significantly increased(P<0.05，P<0.01),however, there was no significant difference in the expression of 5-HT3R protein in Tongxie Yaofang wituout Saposhnikoviae Radix group.Compared with Tongxie Yaofang wituout Saposhnikoviae Radix group,the diarrhea index, fecal water content, 5-HT content, MAO-A enzyme activity, and protein expression of 5-HT3R were significantly decreased in Tongxie Yaofang group and Tongxie Yaofang with double Saposhnikoviae Radix group(P<0.05，P<0.01), and the activity of Na+-K+-ATPase and protein expression of SERT were significantly increased(P<0.05，P<0.01). Conclusion:Saposhnikoviae Radix can enhance the effects of Tongxie Yaofang on improving the water metabolism of rats with IBS-D and regulating the multi-target of 5-HT signaling system, further confirming the synergistic effect of Saposhnikoviae Radix.

Therapeutic effect of adjuvant treatment of acupuncture in a period of day from 7:00 am to 9:00 am on non-dipper essential hypertension / 中国针灸

OBJECTIVE@#To compare the infuences on circadian rhythm of blood pressure in the patients with non-dipper essential hypertension between the combined treatment of time acupuncture and western medication and the simple western medication.@*METHODS@#A total of 70 patients with non-dipper essential hypertension were randomized into an acupuncture plus western medication group (35 cases, 2 cases dropped out) and a western medication group (35 cases). In the western medication group, levamlodipine maleate tablets were taken orally, 2.5 mg each time, once daily. In the acupuncture plus western medication group, on the base of the treatment as the western medication group, acupuncture was applied specially in the period of the day from 7:00 am to 9:00 am. The acupoints included Fengchi (GB 20), Zhongwan (CV 12), Tianshu (ST 25), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), etc. Acupuncture was given once daily, 5 treatments a week. The duration of treatment in the two groups was 4 weeks. The clinic blood pressure before and after treatment, 24 h ambulatory blood pressure and the levels of serum melatonin (MT) and 5-serotonin (5-HT) were observed in the two groups.@*RESULTS@#The total effective rate of anti-hypertension was 75.8% (25/33) in the acupuncture plus western medication group, better than 54.3% (19/35) in the western medication group (<0.05). The 24 h average systolic blood pressure, the daytime average systolic blood pressure, the daytime average diastolic pressure, and the nighttime average systolic blood pressure were all reduced after treatment in the two groups (<0.05). The reduction effect of the aforementioned 4 indexes in the acupuncture plus western medication group was much more obvious as compared with the western medication group (<0.05). After treatment, the serum level of MT was increased and 5-HT decreased in the patients of two groups (<0.05). The serum level of MT in the acupuncture plus western medication group was higher than that in the western medication group and the level of 5-HT was lower than the western medication group (<0.05).@*CONCLUSION@#Time acupuncture therapy in the period of the day from 7:00 am to 9:00 am, combined with western medication effectively reduce blood pressure and regulate the levels of serum MT and 5-HT so as to maintain the circadian rhythm of blood pressure in patients with non-dipper essential hypertension. The therapeutic effect of this combined treatment is superior to simple western medication.

Effect of transcutaneous electrical acupoint stimulation on postoperative analgesia of ureteroscopic holmium laser lithotripsy / 中国针灸

<p><b>OBJECTIVE</b>To explore the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative analgesia of ureteroscopic holmium laser lithotripsy.</p><p><b>METHODS</b>One hundred and twenty adult patients, American Association of Anesthesiologists (ASA) Class Ⅰ or Ⅱ, scheduled to ureteroscopic holmium laser lithotripsy, were randomly assigned into an observation group and a control group, 60 cases in each one. The patients in the observation group were treated with TEAS for postoperative analgesia. TEAS was implemented at bilateral Shenshu (BL 23) and Yinlingquan (SP 9) at the time of back ward and postoperative 4 h, 8 h, 12 h. TEAS at 7:00, 11:00 and 15:00 at the above acupoints were used on the second and third days; while placebo (twice a day, 100 mg a time) was used. Tramadol hydrochloride tablets for postoperative analgesia were applied in the contnol group, twice a day, 100 mg a time, and electrode sheets without stimulation were put on Shenshu (BL 23) and Yinlingquan (SP 9). When analgesia was insufficient with the score of visual analogue scale (VAS)≥3, the patients were treated with tramadol tablets for remedy analgesia. The VAS score, the concentrations of serotonin (5-HT) and substance P (SP) in 3 mL venous blood at the time of back ward (T), postoperative 4 h (T), 12 h (T), 24 h (T), and 48 h (T) were detected respectively. The total amount of medication for remedy analgesia and the incidence of adverse reactions, such as nausea and vomiting within postoperative 48 h were compared between the two groups.</p><p><b>RESULTS</b>The VAS scores at T through T were lower than those at T in the two groups (all <0.05). Compared with the control group, the VAS scores at T through T in the observation group were lower (all <0.05). The total dose of remedy analgesic medicine within 48 h after operation in the observation group was lower than that in the control group (<0.05). Compared with the control group, the concentrations of 5-HT at T, T, T and SP at T through T were lower (all <0.05). The numbers of constipation, nausea and vomiting in the observation group were less than those in the control group (both <0.05).</p><p><b>CONCLUSION</b>TEAS can relieve the pain and reduce the total amount of analgesic medicine, the levels of substance causing pain and the incidence of adverse reactions after ureteroscopic holmium laser lithotripsy.</p>

Efficacy and safety of Duloxetine compared with placebo for diabetic neuropathy pain: meta-analysis.

Background: Duloxetine is relatively considered as a treatment for diabetic neuropathy pain due it is balanced and potent reuptake inhibitor of both serotonin and nor epinephrine where these neurotransmitters play a great in pain inhibition. Materials and Methods: We searched DLX related articles in Pubmed, Cochrane and Embase from 2005 to 2010. 158 articles were found after through search out of which 68 articles were case reports, reviews and meta-analysis, 40 studies were clinical trials but not efficient data was available, 45 studies were RCTs but not related to our topic. Only 5 RCTs included after exclusion. We then performed the meta-analysis of the studies which met our eligibility criteria we performed fixed effect model network meta-analysis to analyze the efficacy of DLX compare to placebo. We chose diabetic neuropathy duration, diabetes mellitus duration, types of diabetes and DLX with regard to MNSI scale. Results: 5 published RCTs were included in this meta-analysis no significant difference observed for DLX and DND [(SD mean difference 0.22 (95%CI -0.16 to 0.60); P=0.25)] , on diabetes mellitus duration for HbA1c and fasting blood glucose (FBG) [(SD mean difference -0.00 (95%CI-0.087 to 0.87); P=1.00)] and on types of diabetes[(COR 1.00 (95% CI 0.73 to 1.38; P=0.98)] and [(OR 1.00 (95% CI 0.72 to 1.37); P=0.98)] .DLX shown to have significant efficacious compared to placebo for MNSI (95% CI -0.37 to – 0.03); P=0.02)]. Conclusion: In the fixed effect model analyses of DLX, showed similar efficacy to placebo for efficacy parameters, except on MNSI scale but not clinically relevant.

Nicergoline improves the depressive behavior of vascular depression in rats by regulating monoamine neurotransmitter receptors expression in hippocampal CA1 region and serum apolipoprotein E4 level / 国际脑血管病杂志

Objective To investigate the effects of nicergoline on expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), D2 dopamine receptor (D2DR),α2A adrenaline receptor (α2AAR) in the hippocampal CA1 region and the serum level of apolipoprotein E4 (ApoE4) in a rat model of vascular depression (VD) . Methods Forty-eight male Sprague-Daw ley rats w ere randomly al ocated into a normal control group, a model group, fluoxetine group, a low-dose nicergoline group, a medium-dose nicergoline group, and a nicergoline high-dose group ( n=8 in each group). A rat model of VD w as induced by the ligation of bilateral common carotid arteries combined w ith chronic unpredictable mild stress (CUMS) plus single housing. The rats did not conduct CUMS or single housing in the normal control group, and the rats in the model group conducted CUMS and single housing. The rats in the fluoxetine group w ere given fluoxetine 1.3 mg/(kg· d) for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The rats in the low -, medium-and high-dose nicergoline groups w ere given nicergoline 0.9, 1.9 and 3.8 mg/(kg· d), respectively for gastric lavage for 3 w eeks at the beginning of CUMS and single housing. The normal control group and the model group w ere given equal volume of distil ed w ater for gastric lavage, once a day for 3 w eeks. Depression-like behavior w as evaluated using sucrose solution consumption and open-field test. Immunohistochemical staining and Western blot were used to detect the expressions of 5-HT1AR, D2DR, andα2AAR in the hippocampal CA1 region. Enzyme linked immunosorbent assay w as used to detect serum ApoE4 level. Results Before CUMS, the scores of horizontal and vertical movement and sucrose solution consumption in the model group, the fluoxetine group and each nicergoline group w ere decreased significantly compared w ith the normal control group (al P<0.01);w hile at 21 days after CUMS, those in the fluoxetine group and the nicergoline medium-and high-dose groups w ere significantly higher than those in the model group (al P<0.05). There w ere no significant differences betw een the fluoxetine group and each nicergoline group. The expression levels of 5-HT1A R, D2DR, α2A AR, and the serum ApoE4 in the model group, the fluoxetine group, and each nicergoline group w ere significantly higher than those in the normal control group. Those of the fluoxetine group and the nicergoline medium -and high-dose groups were significantly lower than the model group (al P<0.01), while there were no significant differences betw een the fluoxetine group and each nicergoline group. Conclusions Nicergoline can improve the depression-like behavior in VD rats. Its mechanism may be associated w ith the dow nregulation of 5-HT1AR, D2DR, α2AAR expressions and serum ApoE4 level.

Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer / 부인종양

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Effect of Raw Atractylodes macrocephala on Motility and 5-HT4 Receptor in Small Intestine of Model Rats with Plateau Hypoxia / 胃肠病学

Background:Gastrointestinal dysmotility is commonly seen in individuals exposed to acute plateau hypoxia. Its pathogenic mechanism is still not clear and intervention study is rarely performed. Aims:To investigate the influence of plateau hypoxia on small intestinal motility of rats,its possible mechanism,and the intervention effect of raw Atractylodes macrocephala. Methods:Seventy Wistar rats were randomly divided into 7 groups:control group,two high altitude model groups(3 500 m and 5 000 m),trimebutine and raw Atractylodes macrocephala groups at 3 500 m or 5 000 m altitude. Rats in six experiment groups were placed in a hypobaric chamber mimicking 3 500 m or 5 000 m altitude and given trimebutine/ raw Atractylodes macrocephala/ saline intragastrically for 3 days. Then all the rats were lavaged with 2 mL ink and sacrificed 30 minutes later. The propulsion rate of ink in small intestine was measured,the pathological changes of small intestine tissue were examined,and the expression of 5-HT4 receptor was determined by immunohistochemistry. Results:Compared with control group,the propulsion rate of small intestine and immunopositive area of 5-HT4 receptor were reduced in model group at 3 500 m altitude,while those in model group at 5 000 m altitude were increased(P ﹤0. 05). Moderate-to-severe mucosal injury was observed in two model groups. In model rats treated with raw Atractylodes macrocephala,the abnormalities in small intestine propulsion and 5-HT4 receptor induced by high altitude(3 500 m and 5 000 m)returned to the control level(P ﹤ 0. 05),and the mucosal injury ameliorated simultaneously. Efficacy of raw Atractylodes macrocephala was prior to trimebutine,a positive control. Conclusions:Acute plateau hypoxia may induce small intestine dysmotility with diverse manifestations,and altitude is a crucial determinant in this process. Raw Atractylodes macrocephala can exert therapeutic effect on this dysmotility by modulating 5-HT4 receptor,and it is also effective in repairing mucosal injury.

Effect of Prucalopride in the Treatment of Chronic Constipation in Asian and Non-Asian Women: A Pooled Analysis of 4 Randomized, Placebo-controlled Studies

BACKGROUND/AIMS: To compare the efficacy and safety of prucalopride, a novel selective high-affinity 5-hydroxytryptamine type 4 receptor agonist, versus placebo, in Asian and non-Asian women with chronic constipation (CC). METHODS: Data of patients with CC, receiving once-daily prucalopride 2-mg or placebo for 12-weeks, were pooled from 4 double-blind, randomized, phase-III trials (NCT00488137, NCT00483886, NCT00485940 and NCT01116206). The efficacy endpoints were: average of > or = 3 spontaneous complete bowel movements (SCBMs)/week; average increases of > or = 1 SCBMs/week; and change from baseline in each CC-associated symptom scores (bloating, abdominal pain, hard stool and straining). RESULTS: Overall, 1,596 women (Asian [26.6%], non-Asian [73.4%]) were included in this analysis. Significantly more patients in the prucalopride group versus placebo experienced an average of > or = 3 SCBMs/week in Asian (34% vs. 11%, P or = 1 SCBMs/week from baseline was significantly higher in the prucalopride group versus placebo among both Asian (57.4% vs. 28.3%, P < 0.001) and non-Asian (45.3% vs. 24.0%, P < 0.001) subgroups. The difference between the subgroups was not statistically significant. Prucalopride significantly reduced the symptom scores for bloating, hard stool, and straining in both subgroups. CONCLUSIONS: Prucalopride 2-mg once-daily treatment over 12-weeks was more efficacious than placebo in promoting SCBMs and improvement of CC-associated symptoms in Asian and non-Asian women, and was found to be safe and well-tolerated. There were numeric differences between Asian and non-Asian patients on efficacy and treatment emergent adverse events, which may be partially due to the overlap with functional gastrointestinal disorders in non-Asian patients.

Experimental study of 5-hydroxytryptamine 1A receptor agonist to improve the voiding dysfunction in diabetic rats / 中华泌尿外科杂志

Objective To investigate the effect of 5-hydroxytryptamine 1A (5-HT1A) receptor agonists to improve micturition function in rats with diabetes mellitus (DM).Methods Fourteen female SD rats with the weight of 250 to 275 g were used.Seven rats were in the DM model group with intraperitoneal injection streptozotocin (STZ,65 mg/kg).Rats in the control group and DM group were anesthetized with urethane (1.3 g/kg) 8 weeks later.A polyethylene (PE)-50 catheter were placed in the left jugular vein for intravenous drug administration.A PE-90 catheter was inserted into the bladder,with the other end connected to a syringe pump for continuous infusion of saline and a pressure transducer for intravesical pressure monitor.Dose-response curves for 8-OH-DPAT were followed by WAY-100635 test.The capacity,residual volume,micturition volume,and EUS-EMG were measured.Results Compared to normal control,DM rats had a higher bladder capacity,residual volume,and a lower voiding efficiency.With increasing dose of 8-OH-DPAT (0.003-1.000 mg/kg,i.v.),the micturition volume increased from (2.15±0.49) ml to (2.85±0.21) ml,the residual volume decreased from (3.40±0.74)ml to (1.82±0.48) ml and voiding efficiency changed from (39.0±9.3)％ to (61.6±6.9)％.Control rats showed little change in cystometic variable.During the micturition,there was a dose-dependent increased phasic EUS activity correlated with the improved voiding efficiency.WAY-100635 (0.300 mg/kg,i.v.) reversed the 8-OH-DPAT-induced changes.Conclusions Both the bladder voiding efficiency and the periodic EUS activity decrease in DM rats.5-HT1A receptor agonist could promote periodic EUS activity and improve voiding efficiency.

Effects of Ramosetron on Gastrointestinal Transit of Guinea Pig

BACKGROUND/AIMS: A selective 5-hydroxytryptamine (5-HT) type 3 receptor antagonist, ramosetron, inhibits stress-induced abnormal defecation in animals and is currently used as a therapeutic drug for irritable bowel syndrome with diarrhea. The aim of this study is to investigate the effect of ramosetron on altered gastrointestinal (GI) transit. METHODS: Male guinea pigs weighing approximately 300 g were used. The effect of ramosetron was investigated on altered GI transit induced by thyrotropin-releasing hormone (TRH), 5-HT, or mustard oil (MO). GI transit was evaluated by the migration of charcoal mixture from the pylorus to the most distal point, and expressed as a percentage (%) of charcoal migration (cm) of the total length of total small intestine (cm). RESULTS: The average charcoal transit was 51.3 +/- 20.1% in the control (vehicle) group, whereas in the ramosetron group charcoal moved 56.6 +/- 21.9%, 46.9 +/- 9.14% and 8.4 +/- 5.6% of the total small intestine at the concentrations of 10, 30 and 100 microg/kg, respectively. GI transit after administration of TRH (100 microg/kg), 5-HT (10 mg/kg) or MO (10 mg/kg) was accelerated compared to vehicle (5-HT, 94.9 +/- 9.22%; TRH, 73.4 +/- 14.7%; MO, 81.0 +/- 13.7%). Ramosetron inhibited GI transit altered by 5-HT, TRH or MO. CONCLUSIONS: Ramosetron modulated GI transit. We suggest that ramosetron may be therapeutically useful for those with accelerated upper GI transit.

Effects of Mosapride on capsule endoscopy in elderly patients / 中华老年医学杂志

Objective To explore the effect of oral mosapride on gastrointestinal transit time in elderly patients undergoing capsule endoscopy.Methods A total of 61 patients referred for capsule endoscopy during 2010 September to 2012 January were involved in this study.40 patients over 65 years old were prospectively randomized into mosapride citrate group (n=19) or non-mosapride citrate group (n=21).Patients under 65 years old were in control group (n=21).Mosapride citrate group took 10 mg mosapride citrate orally before endoscopy.The gastrointestinal transit time was calculated.Results Gastric emptying time and small intestinal transit time of patients over 65 years old were significantly shorter in mosapride citrate group than in non-mosapride citrate group [(48.6± 21.1) minand (64.3±22.4) min,t=2.274,P=0.029; (302.2±67.6) min vs.(347.14±51.18) min,t=2.384,P=0.022].There were on significant differences in gastric emptying time and small intestinal transit time between non-older group [(45.4 ± 28.4) min and (284.8 ± 78.3) min] and mosapride citrate group (t=0.407,P=0.686;t=0.751,P=0.457).There was a difference in the image score between medication group and no medication group (4.94±0.63 versus 4.50±0.68; t=2.137,P=0.039) in over 65 years old patients.Conclusions Mosapride may decreased the gastric emptying time and small intestinal transit time,improves the capsules endoscopy image quality and testing completion rate.

Polymorphisms in the 5-HTR2A gene related to obstructive sleep apnea syndrome / Polimorfismos no gene HTR2A relacionados à síndrome da apneia obstrutiva do sono

Obstructive sleep apnea syndrome (OSAS) is one of the most complex disorders of sleep; it involves several genetic factors that contribute to the phenotype. Serotonin (5-HT) regulates a variety of visceral and physiological functions, including sleep. Gene 5-HTR2A polymorphisms may change the transcription of several receptors in the serotoninergic system, thereby contributing to OSAS. AIM: To investigate the prevalence of T102C and -1438G/A polymorphisms in the 5-HTR2A gene of patients with and without OSAS . MATERIAL AND METHOD: A molecular study of 100 index-cases and 100 controls of both genders. DNA was extracted from blood leukocytes samples and the regions that enclose both polymorphisms were amplified with PCR-RFLP. STUDY DESIGN: A cross-sectional case study. RESULTS: There was a significant prevalence of males in index cases compared to controls (p<0.0001). No significant genotypic differences between cases and controls were found in T102C polymorphisms (p=1.000).There were significant differences between the AA genotype of -1438G/A polymorphisms and patients with OSAS (OR:2.3; CI95 percent:1.20-4.38, p=0.01). CONCLUSION: Serotonergic mechanisms may be related to OSAS. There were no differences in the prevalence of T102C polymorphisms in patients with OSAS and the control group. There is evidence of an association between the -1438G /A polymorphism and OSAS.

A síndrome da apneia obstrutiva do sono (SAOS) é um dos distúrbios mais complexos do sono, envolvendo múltiplos fatores genéticos contribuintes para o fenótipo. A serotonina (5-HT) está envolvida na regulação de uma variedade de funções viscerais e fisiológicas, inclusive o sono. Polimorfismos no gene 5-HTR2A podem alterar a transcrição, afetando o número de receptores do sistema serotoninérgico, contribuindo para a SAOS. OBJETIVO: Investigar a prevalência dos polimorfismos T102C e -1438G/A no gene HTR2A em pacientes com e sem SAOS. MATERIAL E MÉTODO: Estudo molecular em 100 pacientes como casos-índice e em 100 como grupo controle, de ambos os gêneros. O DNA foi extraído de leucócitos de sangue periférico e realizada a amplificação das regiões que abrangem ambos os polimorfismos pelas técnicas da PCR-RFLP. DESENHO DO ESTUDO: Estudo de caso/controle em corte transversal. Resultados: Houve prevalência significativa do gênero masculino nos casos-índice em relação aos controles (p<0,0001). Para o polimorfismo T102C, não houve diferença genotípica significante entre casos e controles (p=1,000). Houve diferença significativa entre o genótipo AA do polimorfismo -1438G/A e pacientes com SAOS (OR:2,3; IC95 por cento:1,20-4,38; p=0,01). CONCLUSãO: Os mecanismos serotoninérgicos parecem estar relacionados a SAOS. Não há diferenças na prevalência do polimorfismo T102C entre os pacientes com SAOS e o grupo controle. Há evidências de associação entre o polimorfismo -1438G/A e a SAOS.

Serotonina e controle hipotalâmico da fome: uma revisão / Serotonin and hypothalamic control of hunger: a review

Este trabalho revisa a participação do sistema serotonérgico no controle da ingestão de alimentos e saciedade. É de grande interesse compreender a relevância desse sistema para o controle fisiológico do balanço energético e da obesidade. Mais de 35 anos de pesquisas sugerem que a serotonina (5-HT) desempenha um importante papel na saciedade. Assim, o sistema serotonérgico tem sido um alvo viável para o controle de peso. A 5-HT apresenta controle sobre a fome e a saciedade através de diversos receptores, com diferentes funções. O receptor 5-HT2C parece ser o mais importante na relação entre ingestão alimentar e balanço energético. Nesta revisão serão discutidos os mecanismos do sistema serotonérgico envolvidos no controle da ingestão de alimentos e saciedade.

This paper reviews involvement of the serotonergic system in the control of food intake and satiety. It is of great interest to understand the relevance of this system for physiological control of energy balance and obesity. Over 35 years of research suggest that serotonin (5-HT) plays an important role in satiety. Thus, the serotonergic system has been a viable target for weight control. The 5-HT has control over hunger and satiety through different receptors with distinct functions. The 5-HT2C receptor may be more important in the relationship between food intake and energy balance. This review will discuss the mechanisms of the serotonergic system involved in the control of food intake and satiety.

Smoking Behavior and Loudness Dependence of the Auditory Evoked Potential among Male Patients with Major Depressive Disorder / 대한정신약물학회지

OBJECTIVE: The loudness dependence of the auditory evoked potential (LDAEP) has been known as an indicator of central serotonergic neurotransmission. Nicotine increases the release of serotonin levels. The current study investigated whether cigarette smoking would make difference in LDAEP among male patients with major depressive disorder. METHODS: Twenty-four non-smoking and 20 smoking male patients meeting DSM-IV criteria for major depressive disorder (MDD) were recruited. There was no significant difference in severity of MDD symptoms between the two groups. The age of participants ranged from 20 to 65 years old. Event-related potentials (ERP) N100 were measured on 5 different sounds (55, 65, 75, 85, 95 dB) and on 5 electrodes (Fz, Cz, Pz, C5, C6). The N1/P2 peak to peak amplitudes and amplitude slope according to 5 different sounds were calculated. RESULTS: LDAEP was significantly weaker in the smoking group in comparison to the non-smoking group (p<0.05). Among non-smoking group LDAEP was negatively correlated with a core depression subscale of Hamilton Rating Scale for Depression (HAM-D) (r=-0.41, p<0.05). CONCLUSION: LDAEP of the smoking patients with MDD group was weaker than the non-smoking patient with MDD group's. This result suggests that smoking may have increased the release of serotonergic neurotransmission in patients with MDD. Future studies need to examine LDAEP changes before and after tobacco use among smoking patients.

Relationship between 5-hydroxytryptamine 1A receptor and G-protein β3 subunit polymorphisms and post-stroke depression / 中华神经科杂志

Objective To assess whether 5-HTR1A C( - 1019) G and GNβ3 C825T gene polymorphisms are associated with post-stroke depression (PSD) and explore the genetic mechanism of the pathogenesis of post-stroke depression. Methods All 159 patients with first stroke were divided into the PSD group and the control group according to HAMD scores. Their genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Results The frequency of 5-HTR1A (-1019) GG genotype(8/53,15. 1% ), G allele (44/106,41.5%)and GNβ3 825T allele(68/106,64. 2% ) were significantly higher in the post-stroke depression group than in the controls (5/106,4.7% ;35/212, 16. 5%; 113/212, 53.3%; ×2 = 23.204, 23. 655, 3. 392, all P ＜ 0. 05 ). Combined genotype analysis showed that individuals with both 5-HTR1A ( - 1019) G and GNβ3 825T allele ( OR =4. 980,95% CI 2. 429-10. 210,P =0. 000) had a higher risk than those with 5-HTR1 A (-1019) G allele ( OR = 3. 589,95% CI 2. 113-6. 096, P = 0. 000) or GNβ3 825T allele ( OR = 0. 638,95% CI 0.395-1. 031 ,P =0. 042) only for post-stroke depression. Conclusion The 5-HTR1A C( - 1019)G and GNβ3 C825T polymorphisms are predisposing genes of post-stroke depression. Our data also suggest a significant interaction between the 5-HTR1A ( - 1019)G allele and GNβ3 825T allele in post-stroke depression.

Change in the expression of hippocampal neuronal 5-hyroxytryptamine1A receptor in a mouse model of chronic restraint stress / 中华麻醉学杂志

Objective To investigate the change in expression of hippocampal neuronal 5-hyroxytryptamine1A(5-HT1A) receptor in a mouse model of chronic restraint stress.Methods Forty BALB/c male mice aged 6-9 months weighing 25-35 g were randomly divided into 2 groups ( n =20 each): normal control group (group C) and chronic restraint stress group( group S).In group S,the model of chronic restraint stress was established described by Wood et al.Tail suspension test,light-dark test and Morris water maze test were performed respectively at 1 d after successful establishment of the model.Immobility time,staying time in light compartment,and escape latency and frequency of crossing the original platform were recorded respectively in tail suspension test,light-dark test and Morris water maze test.Then the animals were sacrificed,hippocampi were removed for determination of the expression of 5-HT1A receptor in CA1 and CA3 regions of hippocampal neurons by immuno-histochemistry.ResultsCompared with group C,immobility time and escape latency were significantly prolonged,staying time in light compartment was shortened,frequency of crossing the original platform was decreased,and the expression of 5-HT1A receptor in hippocampal neurons was down-regulated in group S ( P ＜ 0.05 or 0.01 ).ConclusionChronic restraint stress can induce cognitive impairment in mice by down-regulating the expression of 5-HT1A receptor in hippocampal neurons.