http://www.cnr.it/ontology/cnr/individuo/prodotto/ID314944
Hydroxylated biphenyl derivatives are positive modulators of human GABAA receptors (Articolo in rivista)
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- Label
- Hydroxylated biphenyl derivatives are positive modulators of human GABAA receptors (Articolo in rivista) (literal)
- Anno
- 2012-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1016/j.ejphar.2012.07.048 (literal)
- Alternative label
Mascia, Maria Paola; Fabbri, Davide; Dettori, Maria Antonietta; Ledda, Giovanni; Delogu, Giovanna L.; Biggio, Giovanni (2012)
Hydroxylated biphenyl derivatives are positive modulators of human GABAA receptors
in European journal of pharmacology
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Mascia, Maria Paola; Fabbri, Davide; Dettori, Maria Antonietta; Ledda, Giovanni; Delogu, Giovanna L.; Biggio, Giovanni (literal)
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- http://www.scopus.com/record/display.url?eid=2-s2.0-84866275475&origin=inward (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
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- CNR, IN
CNR, ICB
Università degli Studi di Cagliari (literal)
- Titolo
- Hydroxylated biphenyl derivatives are positive modulators of human GABAA receptors (literal)
- Abstract
- 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 5HT(3A) receptor was partially inhibited by all compounds tested, however this inhibition occurred at relatively high concentrations (100 ?M). All compounds, with the exception of compound 6, potentiate the action of gamma-aminobutyric acid (GABA)-evoked Cl(-) currents in Xenopus laevis oocytes expressing recombinant human ?(1)?(2)?(2L) GABA(A) receptors. Compounds 1, 2, 5 and 7 enhance the function of the GABA(A) receptor at concentrations higher than 3-10 ?M. Compound 4 was the most efficacious. However, compound 3 was the most potent (EC(50) 0.8 ?M). The potency of compound 3 in modulating the function of the GABA(A) receptor was comparable to that of diazepam, propofol or allopregnanolone. The enhancement of the GABA evoked Cl(-) 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 GABA(A) receptor. (literal)
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