کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829148 | 1558988 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hydroxylated biphenyl derivatives are positive modulators of human GABAA receptors
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
A series of 7 hydroxylated biphenyl derivatives (1-7) were prepared to evaluate their ability to modulate the function of several ligand gated ion channel (LGIC) recombinant receptors expressed in Xenopus laevis oocytes. Compounds 1, 3, 4, 6 and 7 are natural occurring compounds whereas the synthesis of compounds 2 and 5 was previously reported (Delogu et al., 2004, Fabbri et al., 2007). None of the compounds tested were able to modify, the activity of the strychnine-sensitive glycine receptor, or the activity of nicotinic receptor. The function of the 5HT3A receptor was partially inhibited by all compounds tested, however this inhibition occurred at relatively high concentrations (100 μM). All compounds, with the exception of compound 6, potentiate the action of gamma-aminobutyric acid (GABA)-evoked Clâ currents in Xenopus laevis oocytes expressing recombinant human α1β2γ2L GABAA receptors. Compounds 1, 2, 5 and 7 enhance the function of the GABAA receptor at concentrations higher than 3-10 μM. Compound 4 was the most efficacious. However, compound 3 was the most potent (EC50 0.8 μM). The potency of compound 3 in modulating the function of the GABAA receptor was comparable to that of diazepam, propofol or allopregnanolone. The enhancement of the GABA evoked Clâ currents by compound 3 was not affected by flumazenil. Compound 3 did not induce loss of the righting reflex in rats suggesting that it is not an anesthetic agent, however, its ability in protecting the animals from seizures induced by picrotoxin confirm that its action occurs through the GABAA receptor.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 693, Issues 1â3, 15 October 2012, Pages 45-50
Journal: European Journal of Pharmacology - Volume 693, Issues 1â3, 15 October 2012, Pages 45-50
نویسندگان
Maria Paola Mascia, Davide Fabbri, Maria Antonietta Dettori, Giovanni Ledda, Giovanna Delogu, Giovanni Biggio,