Tracazolate hydrochloride

Tracazolate hydrochloride (ICI 136753 hydrochloride) is a potent GABAA receptor modulator. Tracazolate hydrochloride potentiates α1β1γ2s (EC50=13.2 μM) and α1β3γ2 (EC50=1.5 μM) in a concentration-dependent manner. Tracazolate hydrochloride has the potency (EC50) is determined by the nature of the third subunit (γ1-3, δ, ε) within the receptor complex. Tracazolate hydrochloride possesses anxiolytic and anticonvulsant activity[1][2].

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

GABAA[1]

Tracazolate hydrochloride (ICI 136753 hydrochloride) inhibits α1β1ε and α1β3ε GABAA receptors with IC50s of 4.0 μM, 1.2 μM, respectively. Replacement of Ser265 within the β1 subunit with Asn (the β3 counterpart) increases the sensitivity of tracazolate, whereas the opposite mutation (Asnβ3 to Ser) decreases the sensitivity to Tracazolate[1]. Tracazolate hydrochloride (10 μM) increases the maximum current amplitude and enhances the sensitivity of α1β2δ-containing GABAA receptors in oocytes[2].

[1]. Sally-Anne Thompson, et al. Tracazolate reveals a novel type of allosteric interaction with recombinant gamma-aminobutyric acid(A) receptors. Mol Pharmacol. 2002 Apr;61(4):861-9.

[2]. N Zheleznova, et al. alpha1beta2delta, a silent GABA_A receptor: recruitment by tracazolate and neurosteroids. Br J Pharmacol. 2008 Mar;153(5):1062-71.