An Overview of the CNS-Pharmacodynamic Profiles of Nonselective and Selective GABA Agonists

Table 1

In vitro pharmacological property of the GABAergic compounds.

Compound	𝛼1		𝛼2		𝛼3		𝛼5		𝛼1/𝛼2-ratio
	𝐾𝑖 (nM)	Efficacy° (%)	𝐾𝑖 (nM)	Efficacy°(%)	𝐾𝑖 (nM)	Efficacy°(%)	𝐾𝑖 (nM)	Efficacy° (%)
TPA023* [26]	0.27	0^#	0.31	11	0.19	21	0.41	5	0
TPACMP2* [13]	0.22	18	0.40	23	0.21	45	0.23	18	0.78
SL65.1498^# [28]	17	45	73	115	80	83	215	48	0.39
Zolpidem	20 [29]	75^§ [30]	400 [29]	78^§ [30]	400 [29]	80^§	5000 [29]	9^§ [30]	0.96

°Relative efficacy is defined as the extent of the potentiation of GABA-A EC20-equivalent current produced by the compound compared to that produced by a nonselective full agonist (chlordiazepoxide/diazepam).
*Mean values of 3 experiments in Xenopus oocytes with human recombinant αβ3γ2 receptors; efficacy relative to chlordiazepoxide.
^#Mean values of 3 experiments in hek293 cells with recombinant rat receptors αβ2γ2; efficacy relative to chlordiazepoxide.
^§Mean values of 3 experiments in Xenopus oocytes with human recombinant αβ2γ2 receptor; efficacy relative to diazepam.