کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8684347 | 1579885 | 2017 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phenylalanine derivatives with modulating effects on human α1-glycine receptors and anticonvulsant activity in strychnine-induced seizure model in male adult rats
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کلمات کلیدی
GluK1NMDAMBSAMPAnAChR6-HydroxydopamineN-methyl-d-aspartic acidSTRVPAHEK-293DMEM6-OHDAAEDDMSO - DMSOROS - ROSAdenosine Triphosphate - آدنوزین تری فسفاتATP - آدنوزین تری فسفات یا ATPStrychnine - استریچنینیInhibitor - بازدارندهBAPTA - بیایپیتیایanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of variancePotentiator - توانمندسازantiepileptic drug - داروهای ضدصرعDopamine - دوپامینDimethylsulfoxide - دیمتیل سولفواکسیدhuman embryonic kidney cell line - سلول انسانی جنین انسانAnticonvulsant - ضد انعقادDulbecco’s modified eagle’s medium - محیط عقاب اصلاح شده DulbeccoValproic acid - والپروات و والپروات سدیم یا والپروئیک اسیدKainite - کاینیتradical oxygen species - گونه های اکسیژن رادیکالnicotinic acetylcholine receptor - گیرنده استیلکولین نیکوتین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Phenylalanine derivatives with modulating effects on human α1-glycine receptors and anticonvulsant activity in strychnine-induced seizure model in male adult rats Phenylalanine derivatives with modulating effects on human α1-glycine receptors and anticonvulsant activity in strychnine-induced seizure model in male adult rats](/preview/png/8684347.png)
چکیده انگلیسی
The critical role of α1-glycine receptor (α1-GLYRs) in pathological conditions such as epilepsy is well known. In the present study, structure-activity relations for a series of phenylalanine derivatives carrying selected hydrogen bond acceptors were investigated on the functional properties of human α1-GLYR expressed in Xenopus oocytes. The results indicate that one particular substitution position appeared to be of special importance for control of ligand activity. Among tested ligands (1-8), the biphenyl derivative (2) provided the most promising antagonistic effect on α1-GLYRs, while its phenylbenzyl analogue (5) exhibited the highest potentiation effect. Moreover, ligand 5 with most promising potentiating effect showed in-vivo moderate protection when tested in strychnine (STR)-induced seizure model in male adult rats, whereas ligand 2 with highest antagonistic effect failed to provide appreciable anti(pro)convulsant effect. Furthermore, ligands 2 and 5 with the most promising effects on human α1-GLYRs were examined for their toxicity and potential neuroprotective effect against neurotoxin 6-hydroxydopamine (6-OHDA). The results show that ligands 2 and 5 possessed neither significant antiproliferative effects, nor necrotic and mitochondrial toxicity (up to concentration of 50 μM). Moreover, ligand 2 showed weak neuroprotective effect at the 50 μM against 100 μM toxic dose of 6-OHDA. Our results indicate that modulatory effects of ligands 2 and 5 on human α1-GLYRs as well as on STR-induced convulsion can provide further insights for the design of therapeutic agents in treatment of epilepsy and other pathological conditions requiring enhanced activity of inhibitory glycine receptors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Epilepsy Research - Volume 138, December 2017, Pages 124-131
Journal: Epilepsy Research - Volume 138, December 2017, Pages 124-131
نویسندگان
Bassem Sadek, Murat Oz, Syed M. Nurulain, Petrilla Jayaprakash, Gniewomir Latacz, Katarzyna KieÄ-Kononowicz, Ewa SzymaÅska,