The present study investigated the anticonvulsive effect of the disubstituted diaryl diselenides diphenyl diselenide (PhSe)(2), m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on a chemical model of seizure induced by pentylenetetrazole (PTZ) in mice. (PhSe)(2), (p-Cl-C(6)H(4)Se)(2) and (p-CH(3)O-C(6)H(4)Se)(2) did not abolish seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) at the dose of 100 mg/kg significantly prolonged the latency of the onset of the first convulsive episode and reduced the number of animals that presented seizures. To investigate the possible mechanisms involved in the anticonvulsant effect of (m-CF(3)-C(6)H(4)Se)(2), mice were submitted to different associations (all drugs in a sub-effective dose); aminooxyacetic acid hemihydrochloride (AOAA, a gamma-aminobutyric acid (GABA)-T inhibitor), diazepam (a GABA(A) receptor agonist) or DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake) were pre-administered together with (m-CF(3)-C(6)H(4)Se)(2). (m-CF(3)-C(6)H(4)Se)(2) + DABA abolished seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) administered alone or with PTZ decreased the levels of GABA uptake in cerebral cortex slices. The present study demonstrates that (m-CF(3)-C(6)H(4)Se)(2) exerts anticonvulsant action by decreasing the levels of GABA uptake.
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http://dx.doi.org/10.1016/s1734-1140(09)70175-6 | DOI Listing |
Reprod Sci
January 2025
Era College of Pharmacy, Era University, Lucknow, Uttar Pradesh, India.
PCOS is a common endocrine disorder in women particularly in their reproductive age. GABA has been implicated in the pathogenesis of PCOS through its central role in the hypothalamus. Hence, in this study we investigated the effect of Nipecotic acid (NPA) in Letrozole induced PCOS in female Wistar rats as NPA has been proven as a GABA uptake inhibitor.
View Article and Find Full Text PDFFEBS J
January 2025
Department of Pharmacology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany.
Creatine is essential for ATP regeneration in energy-demanding cells. Creatine deficiency results in severe neurodevelopmental impairments. In the brain, creatine is synthesized locally by oligodendrocytes to supply neighboring neurons.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Kazan Institute of Biochemistry and Biophysics, Federal Research Center "Kazan Scientific Center of RAS", 2/31 Lobachevsky Street, P.O. Box 30, Kazan 420111, Russia.
γ-Aminobutyric acid (GABA) has a significant impact on the functioning of not only the central but also the peripheral part of the nervous system. Recently, various elements of the GABAergic signaling system have been discovered in the area of the neuromuscular junction of mammals. At the same time, the functional activity of membrane-bound GABA transporters (GATs) and their role in neuromuscular transmission have not been identified.
View Article and Find Full Text PDFEJNMMI Res
December 2024
Department of Medical Cell Biology, Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Box 571, 75123, Uppsala, Sweden.
Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive β-cell destruction. There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the γ-aminobutyric acid A receptors (GABARs) in pancreatic islets and the fact that GABAR agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [C]flumazenil ([C]FMZ) could serve as a marker of the endocrine mass of the pancreas.
View Article and Find Full Text PDFACS Chem Neurosci
December 2024
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Allopregnanolone (AlloP) is an example of neuroactive steroids (NAS), which is a potent allosteric activator of the γ-aminobutyric acid A (GABA) receptor. The mechanisms underlying the biological activity of AlloP and other NAS are only partially understood. Here, we present intrinsically fluorescent analogs of AlloP (MQ-323) and its 3β-epimer, epi-allopregnanolone (E-AlloP) (YX-11), and show, by a combination of spectroscopic and computational studies, that these analogs mimic the membrane properties of AlloP and E-AlloP very well.
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