A1a | α1βn γ2
| High affinities and efficacies for classical BZ agonists,4-b CL 218872 (partial agonist), zolpidem, 2′-oxoquazepam4-c |
A1b | α1 βnγ3
| Same as for A1a, but ∼400-fold less sensitive to zolpidem and affinities are lower for 2′-oxoquazepam (in the same range as for A2, A3, and A5) and for classical BZ agonists4-d
|
A1c | α1 βn γ1
| Same as for A1b, but flumazenil and Ro 15-4513 have low affinity and act, like β-carbolines (inverse agonists at A1a,b), as low-potency positive agonists4-e |
A2a | α2 βnγ2
| Similar to A3 for the ligands noted there, but other properties not yet defined |
A2c | α2 βnγ1
| BZ/ω agonists have 2- to 20-fold lower potency than on A2a, with FG8205 the most selective. The affinity of zolpidem is 5-fold greater on A2c but with very low efficacy. Insensitive to antagonists (e.g., flumazenil, CGS-8216, and Ro 15-4513). DMCM is an agonist4-f |
A3a | α3 βnγ2
| High affinities and potencies for classical BZ agonists and β-carbolines, similar to those of A1, but intermediate for zolpidem, for CL 218872 and 2′-oxoquazepam, ∼10-fold lower than on A1a4-g |
A4a | α4 βnγ2
| Insensitive to classical BZ agonists, zolpidem and many other BZ/ω agonists. Notable exceptions are bretazenil, CGS 20625, and some pyrazoloquinolines. Intermediate affinities for most β-carboline inverse agonists (∼10 times higher than at α6 βn γ2), but high affinity for DMCM. Flumazenil and Ro 15-4513 are agonists. The direct activation by propofol or pentobarbital is absent4-h |
A5a1 | α5β1/3 γ2
| A5: High affinity for classical benzodiazepine agonists but insensitive to imidazopyridines. Intermediate affinity for CL218872 and 2′-oxoquazepam. Certain 8-acetylenic imidazobenzodiazepines (inverse agonists) and L-655,708 (BZ/ω agonist) are highly selective |
A5b3 | α5β3 γ3
| Affinities of A5b3 are as for A5a1, but triazolam and β-carbolines are ∼10- to 30-fold weaker and CL 218872 is 10-fold stronger |
A5a2 | α5 β2γ2
| A5a1 differs from A5a2 in its outward rectification and its slower desensitization at depolarized voltages4-i
|
A6a1 | α6 β1γ2
| Insensitive to all BZ/ω ligands except bretazenil and some other partial agonists; flumazenil and Ro 15-4513 become partial agonists and DMCM an antagonist (fig. 5) |
A6a2 | α6β2/3 γ2
| Same as for A6a1, but A6a2 is antagonized selectively by furosemide (see notes to table 1) |
A16a2 | α6α1 β2/3γ2
| Combines the binding sites of A1a and A6a24-j
|
A0r | | A0r: insensitive to all BZ/ω ligands, but also to bicuculline and pentobarbital. Not activated by isoguvacine |
A0r1 | ρ1 |
A0r2 | ρ2
|
A0r12 | ρ1ρ2
| A0r12 (alone) has very low sensitivity to picrotoxin (in the rat) (for references: see Sections I.A. and IV.D.) |
A0r3 | ρ3 |
A01, A02 | | Insensitive to all BZ/ω ligands, not because of ρ, but (e.g.) α + β + δ or α + β + ε. Sensitive to bicuculline |
A01 | α1 βn δ | Same as above, and highly sensitive to zinc |
A04 | α4βn δ | Generally similar to A01 |
A06 | α6βn δ | Same as for A01; in cerebellar granule cells only4-k |
A01e | α1 βn ε | Generally similar to A01 |