Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABA_A Receptor Modulators?

Table 2

Summary of novel GABA_A receptor subtype selective compounds.

Target	Name	Efficacy; (compared to a classical benzodiazepine)	Affinity/Remarks	Ref
α 1	Zolpidem	Comparable at α 1/α 2/α 3/α 5	5-10-fold higher affinity for α 1 versus α 2/3 > 1000 fold higher affinity for α 1 versus α 5	[15]
α 2/3	TPA023	α 1 (0%), α 2 (11%), α 3 (21%), α 5 (5%)	Equivalent affinity	[8]
α 2/3	TPA123	α 1 (23%), α 2 (35%), α 3 (43%), α 5 (19%)	Equivalent affinity. Reinforcing efficacy and physiological dependence remained present	[8]
α 2/3	L838,417	α 1 (1.5%), α 2 (43%), α 3 (43%), α 5 (39%)	Equivalent affinity	[23]
α 2/3	SL651498	α 1 (45%), α 2 (115%), α 3 (83%), α 5 (50%); Compared to zolpidem for α 1 efficacy	5–10-fold increased affinity for α 2/3, 10–20 fold lower affinity for α 5	[31]