Positive allosteric modulation of the GHB high-affinity binding site by the GABAA receptor modulator monastrol and the flavonoid catechin

Flavonoid nutraceuticals and ionotropic receptors for the inhibitory neurotransmitter GABA

“…2), which is identical to (þ)-catechin except that it has a ketone in the 4 position, was a negative modulator of GABA A receptors (Eghorn et al, 2014). The closely related dihydromyricetin (Fig.…”

“…2), an important constituent of chocolate and many other foodstuffs (Arts et al, 2000), is an allosteric agonist at recombinant a4b3d GABA A receptors expressed in oocytes (Eghorn et al, 2014). (þ)-Catechin appears to be a positive allosteric modulator for the high-affinity binding of g-hydroxybutyric acid (GHB) on these receptors.…”

Metal Complexes of Flavonoids: Their Synthesis, Characterization and Enhanced Antioxidant and Anticancer Activities

“…It was not until the 1990's that research on flavonoids witnessed significant progress, with the number of publications increasing by approximately 6-fold, from 524 in 1990 to 3147 in 2017. As a result it is now well established that flavonoids have a wide and diverse range of biological activities [2,3] such as anti-viral [4][5][6], anti-bacterial [7][8][9][10], neuroprotective [11][12][13], cardioprotective [14,15], anti-oxidant [16][17][18] and anti-cancer [3,19,20] properties. With respect to the beneficial health effects of flavonoids, the greatest impact has been seen within the anti-cancer field [2].…”

Structure-Dependent Activity of Natural GABA(A) Receptor Modulators

“…(+)- and (−)-catechin ( 82 and 83 ) have been tested for their effect on [ 3 H]γ-hydroxybutyric acid (GHB) binding and on the binding of [ 3 H]NCS-382, a GHB antagonist in order to find new lead compounds for the GHB high-affinity site of the GABA(A) receptor [ 76 ]. (+)-catechin enhanced [ 3 H]NCS-382 binding to 163% and decreased [3H]GHB-binding to 54%, whereas (−)-catechin was less active.…”