The diuretic bumetanide decreases autistic behaviour in five infants treated during 3 months with no side effects

Lemonnier, Éric; Ben-Ari, Yehezkel

doi:10.1111/j.1651-2227.2010.01933.x

Cited by 125 publications

(106 citation statements)

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“…Currently, bumetanide is under study in a phase I/II clinical trial as a single add-on therapy to existing phenobarbital treatment for neonatal seizures in infants 33-44 wks of age at dosages of 0.1-0.3 mg/kg (clinicaltrials.gov, NCT00830531). Interestingly, autistic behaviors, one of the developmental outcomes associated with PVL in survivors of preterm birth, have been shown to decrease in a small cohort of human subjects following bumetanide treatment (16,17); bumetanide treatment has also been shown to restore abberant behavior and brain oscillations in animal models of autism when given prenatally (18).…”

Section: Bumetanide Protection In Rodent Pvlmentioning

confidence: 99%

Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter injury in a rodent model of periventricular leukomalacia

Jantzie

Park

et al. 2015

Pediatr Res

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Background: Periventricular leukomalacia (PVL) is a major form of preterm brain injury. Na + -K + -Cl − 1 cotransporter (NKCC1) expression on neurons and astrocytes is developmentally regulated and mediates Cl − reversal potential. We hypothesized that NKCC1 is highly expressed on oligodendrocytes (OLs) and increases vulnerability to hypoxia-ischemia (HI) mediated white matter injury, and that the NKCC1 inhibitor bumetanide would be protective in a rodent PVL model. Methods: Immunohistochemistry in Long-Evans rats and PLP-EGFP transgenic mice was used to establish cell-specific expression of NKCC1 in the immature rodent brain. HI was induced on postnatal day 6 (P6) in rats and the protective efficacy of bumetanide (0.3 mg/kg/i.p. q12h × 60 h) established. results: NKCC1 was expressed on OLs and subplate neurons through the first 2 postnatal weeks, peaking in white matter and the subplate between P3-7. Following HI, NKCC1 is expressed on OLs and neurons. Bumetanide treatment significantly attenuates myelin basic protein loss and neuronal degeneration 7 d post-HI. conclusion: Presence and relative overexpression of NKCC1 in rodent cerebral cortex coincides with a period of developmental vulnerability to HI white matter injury in the immature prenatal brain. The protective efficacy of bumetanide in this model of preterm brain injury suggests that Cl − transport is a factor in PVL and that its inhibition may have clinical application in premature human infants.

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Section: Bumetanide Protection In Rodent Pvlmentioning

confidence: 99%

Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter injury in a rodent model of periventricular leukomalacia

Jantzie

Park

et al. 2015

Pediatr Res

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“…Shorter sleep onset latency in patients undergoing hyperbaric oxygen treatment doi:10.1111/pcn.12478 I NDIVIDUALS ARE KNOWN to experience sleep disturbances upon ascending to higher altitudes, 1 and during hyperbaric saturation diving experiments. 2 Although sustained barometric changes in either direction appear to cause sleep disturbances, it has been observed that patients who undergo hyperbaric oxygen (HBO 2 ) treatment experience somnolence.…”

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“…1 However, older patients with depression should be carefully evaluated for potential contributors. For example, prodromal dementia with Lewy bodies (DLB) can cause depression several years before the onset of dementia.…”

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“…Therefore, the dopamine full or partial agonist may improve the depressive symptoms of DLB without triggering motor dysfunction. However, aripiprazole augmentation in older depressed patients can cause adverse events of parkinsonism at a high rate (17%), 1 unlike in patients with adult depression (7%) 2 and Alzheimer's disease (5%). This discrepancy has some possible reasons as follows.…”

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Shorter sleep onset latency in patients undergoing hyperbaric oxygen treatment

Uezato

Enomoto

Tamaoka

et al. 2016

Psychiatry Clin Neurosci

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showed that treatment with bumetanide or placebo had no significant effect on BPRS score in patients, F(1, 24) = 0.062, P = 0.805. Similar to previous reports, 2 assessment of treated patients 2 months after bumetanide intake revealed that both bumetanide and placebo had no serious side-effects based on a prepared checklist.These study data have some limitations. First, the effect of bumetanide on patients with schizophrenia was not investigated on a specific symptom. Second, the dose of bumetanide 2 mg/day may be inadequate to show biological effects. Further studies are required to address these issues and to show the actual effect of bumetanide on schizophrenia. Fifteen patients (3 men and 12 women; age: 55.9 AE 13.9 years) receiving HBO 2 treatment for their underlying illnesses (maxillary osteomyelitis, n = 9; radiation injury, n = 2; spinal canal stenosis, n = 4) were recruited to this study after their informed consent was obtained. The anonymity of patients was preserved throughout the study. Sleep quality indices were calculated using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J), 3 the Epworth Sleepiness Scale (JESS), 4 the Visual Analog Scale (VAS), and actigraphy. Each of the 15 subjects was tested before starting the first HBO 2 treatment (pre) and after no more than five (short) treatments. Nine subjects were also tested after 20 (long) HBO 2 treatments. Statistical comparisons were performed using the Wilcoxon Signed Rank test. DISCLOSURE STATEMENTFollowing the short treatment, we observed an overall improvement in sleep indices, as indicated by significant improvements in the total PSQI-J score (pre: 7.7 vs short: 6.3, P = 0.041), in addition to significantly lower sleep onset latency (pre: 1.8 vs short: 1.1, P = 0.013), which was consistent with the actigraphy results (pre: 10.1 min vs short: 6.2 min, P = 0.016). Following the long treatment, we observed significant improvements in the total PSQI-J score (pre: 7.7 vs long: 5.0, P = 0.016), sleep quality (pre: 1.5 vs long: 0.9, P = 0.025), and daytime dysfunctions subscales (pre: 0.7 vs long: 0.3, P = 0.025), as well as in the total JESS score (pre: 8.3 vs long: 5.7, P = 0.037). We used the VAS to assess fatigue and pain, and observed a significant improvement in fatigue after both short (P = 0.009) and long HBO 2 treatments (P = 0.035), and in pain after the long treatment (P = 0.018) but not after the short treatment.With regard to the better sleep indices observed after the long treatments, we cannot exclude the possibility that this improvement is mediated by the alleviation of their original symptoms, primarily pain, rather than having a direct effect on sleep itself. However, the shorter sleep onset latency observed after the short treatment appears to be the immediate effect of HBO 2 treatment rather than an indirect effect, as the pain had not subsided in the short treatment period. Although this preliminary study is limited by the lack of a control group, our findings suggest that HBO 2 is a potential novel therapeu...

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“…Lack of the effect of bumetanide, a selective NKCC1 inhibitor, in patients with schizophrenia: A double-blind randomized trial doi:10.1111/pcn.12475 T HE EXCITATORY FUNCTION of GABA has been reported to contribute to the pathogenesis of some neuropsychological disorders, for example autism 1 and epilepsy. 2 The switch in GABA function, from inhibitory to excitatory, has been attributed to the alteration of cation-chloride cotransporters involved in the regulation of intercellular chloride concentration, chloride-intruder NKCC1 and chlorideextruder KCC2.…”

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Lack of the effect of bumetanide, a selective NKCC1 inhibitor, in patients with schizophrenia: A double‐blind randomized trial

Rahmanzadeh

Shahbazi

Ardakani

et al. 2016

Psychiatry Clin Neurosci

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The diuretic bumetanide decreases autistic behaviour in five infants treated during 3 months with no side effects

Abstract: Bumetanide decreases autistic behaviour with no side effects suggesting that diuretic agents may exert beneficial effects on IAS and that alterations of the actions of GABA may be efficient in IAS treatment calling for large scale randomized trials.

Cited by 125 publications

References 23 publications

Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter injury in a rodent model of periventricular leukomalacia

Chloride cotransporter NKCC1 inhibitor bumetanide protects against white matter injury in a rodent model of periventricular leukomalacia

Shorter sleep onset latency in patients undergoing hyperbaric oxygen treatment

Lack of the effect of bumetanide, a selective NKCC1 inhibitor, in patients with schizophrenia: A double‐blind randomized trial

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