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AA 29504, {2-amino-4-(2, 4, 6-trimethylbenzylamino)-phenyl}-carbamic acid ethyl ester is a positive modulator of extrasynaptic GABAA receptors. AA 29504 is also an analogue of the KCNQ channel opener retigabine with a 3-4 fold lower potency than retigabine. The EC50 of AA 29504 at KCNQ channels is between 9.6 and 13.5 μM [2]. AA 29504 at 1 µM had no agonist activity when tested at α1β3γ2s or α4β3δ GABAA receptors expressed in Xenopus oocytes, but left-shifted the EC50 of GABA and gaboxadol (THIP) at both receptors. The maximum GABA response was unchanged at α1β3γ2s receptors by AA 29504 (1 µM), but increased 3-fold at α4β3δ receptors [1].

GABA transiently activates synaptic GABAA receptors, leading to the classical inhibitory post-synaptic currents (phasic inhibition) [2]. KCNQ (also termed Kv7) channels are voltage-dependent potassium channels composed of homo- and heteromeric complexes of five different KCNQ subunits (KCNQ1–5, or called Kv7.1–Kv7.5) [3].

In Xenopus oocytes, AA 29504 at concentrations below 3 µM exhibited no intrinsic activity, whereas at 3 µM and above AA 29504 could induce a small response, which could not be blocked by bicuculline. Treatment with AA 29504 at a concentration of 1 µM showed no intrinsic activity at GABAA receptors and KCNQ channels, but left-shifted the concentration-response curve of GABA without affecting the maximum response to GABA [1].

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