About 60% of furosemide is absorbed in the intestine, and there are substantial inter- and intraindividual differences in bioavailability (range 10-90%). About 80% of bumetanide is absorbed, and its absorption does not change when it is taken with food. It is said to be a more predictable diuretic, meaning that the predictable absorption is reflected in a more predictable effect. Bumetanide is 40 times more potent than furosemide for people with normal renal function. Synthesis
Bumetanide is synthesized from 4-chlorobenzoic acid. In the first stage of synthesis, it undergoes sulfonylchlorination by chlorosulfonic acid, forming 4-chloro-3-chlorosulfonylbenzoic acid, which is further nitrated with nitric acid to 4-chloro-3-chlorosulfonyl-5-nitrobenzoic acid. Reacting this with ammonia gives 5-aminosulfonyl-4-chloro-3-nitrobenzoic acid, which when reacted with sodium phenolate is transformed into 5-amino-sulfonyl-3-nitro-5-phenoxybenzoic acid. Reduction of the nitro group in this product by hydrogen using a palladium on carbon catalyst gives 3-amino-5-aminosulfonyl-5-phenoxybenzoic acid. Finally, reacting this with butyl alcohol in the presence of sulfuric acid, followed by treatment with sodium hydroxide to hydrolyze the butyl ester, gives the desired bumetanide. Research
In the brain, bumetanide blocks the NKCC1 cation-chloride co-transporter, and thus decreases internal chloride concentration in neurons. In turn, this concentration change makes the action of GABA more hyperpolarizing, which may be useful for treatment of neonatal seizures, which quite often are not responsive to traditional GABA-targeted treatment, such as barbiturates. Bumetanide is therefore under evaluation as a prospective antiepileptic drug.The drug has also been studied as a treatment for autism. References
External links
"Bumetanide". Drug Information Portal. U.S. National Library of Medicine.
He was noted to have unilateral congenital ptosis, clinodactyly affecting the index and ring fingers, bilateral thumb adduction, and upper limb weakness at birth, with symptoms of Hirschsprungs disease showing 24 hours after he was born. He was psychomotorly delayed. CT scans showed brain growth delay, corpus callosum agenesis, and a hypoplastic inferior vermis and cerebellum. Electroencephalograms gave abnormal results. He was born weighing 3.09 kilograms, being 49 cm long, and with a head circumference of 33.5 cm. The second case was his 24-year-old maternal uncle. He was psychomotorly delayed like his nephew, and he noted to have pectus excavatum and speckled irises only. CT scans showed only corpus callosum agenesis. His head circumference at the time was 52 cm. Chromosomal analysis done on the proband child, his mother and his uncle was normal. Family history on the mothers family only revealed a distant third-cousin with Hirschsprungs disease, her two other brothers were normal, and she went on to have a normal female pregnancy. 1992: Kang et al. describes 4 male children each from 4 different sibships belonging to an ethnic Chinese Taiwanese family, constituting the first case report of X-linked complicated corpus callosum dysgenesis in China. Said children had microcephaly, spasticity, intellectual disabilities, hydrocephalus, and facial dysmorphisms. Some of them had an interhemispheric cyst. 2006: Basel-Vanagaite et al. describes 2 Israeli Jewish brothers who both had partial corpus callosum agenesis alongside mild intellectual disability. One of the siblings had bilateral congenital radial head dislocation and Hirschsprungs disease.