Nomenclature |
α4* |
α6* |
α7* |
HGNC, UniProt |
CHRNA4, P43681
|
CHRNA6, Q15825
|
CHRNA7, P36544
|
Commonly used antagonists |
α4β2: DHβE (KB = 0.1 μM; IC50 = 0.08 - 0.9 μM), (+)-tubocurarine (KB = 3.2 μM, IC50 = 34 μM); α4β4: DHβE (KB = 0.01 μM, IC50 = 0.19 – 1.2 μM), (+)-tubocurarine (KB = 0.2 μM, IC50 = 50 μM) |
α6/α3β2β3 chimera: DHβE (IC50 = 1.1 μM) |
(α7)5: DHβE (IC50 = 8 - 20 μM); (α7)5: (+)-tubocurarine (IC50 = 3.1 μM) |
Selective agonists |
TC-2403(Full agonist, α4β2) 232, TC-2559(Full agonist, α4β2) 211
|
– |
4BP-TQS(Full agonist, 4BP-TQS is an allosteric agonist) 215, A-582941(Full agonist, (α7)5) 204, PHA-543613(Full agonist, (α7)5) 239, PHA-709829(Full agonist, (α7)5) 200, PNU-282987(Full agonist, (α7)5) 205, TC-5619(Full agonist, (α7)5) 219
|
Selective antagonists |
– |
α-conotoxin MII (α6β2*), α-conotoxin MII [H9A, L15A] (α6β2β3), α-conotoxin PIA (α6/α3β2β3 chimera) |
α-bungarotoxin ((α7)5), α-conotoxin ArIB ((α7)5), α-conotoxin ImI ((α7)5), methyllycaconitine ((α7)5) |
Selective channel blockers (IC50) |
A-867744(α4β2) 227, NS1738(α4β2) 237, mecamylamine (α4β4) (3.3x10-7 – 4.9x10-6 M), mecamylamine (α4β2) (3.6x10-6 – 4.1x10-6 M), hexamethonium (α4β2) (6.8x10-6 – 2.9x10-5 M), hexamethonium (α4β4) (9.1x10-5 M) |
mecamylamine (α6/α3β2β3 chimera) (1.1x10-5 M), hexamethonium (α6/α3β2β3 chimera) (9.1x10-5 M) |
mecamylamine ((α7)5) (1.56x10-5 M) |
Selective allosteric regulators |
LY2087101(Positive, potentiates α4β2 and α4β4) 206, NS9283(Positive, α4β2 and α4β4) 225
|
– |
A-867744(Positive, (α7)5:Type 2; also blocks α3β4 and α4β2) 227, JNJ1930942 (Positive, (α7)5:Type 1/2) 214, LY2087101(Positive, (α7)5:Type 1) 206, NS1738(Positive, (α7)5:Type 1; also blocks α3β4 and α4β2) 237, PNU-120596(Positive, (α7)5:Type 2) 221
|
Radioligands (Kd) |
[125I]epibatidine (α4β2) (1x10-11 – 3.3x10-11 M), [3H]epibatidine (α4β2) (1x10-11 – 3.3x10-11 M), [3H]cytisine (α4β2) (1x10-10 M - Rat), [3H]cytisine (α4β4) (1x10-10 M), [125I]epibatidine (α4β4) (1.87x10-10 M), [3H]epibatidine (α4β4) (1.87x10-10 M), [125I]epibatidine (α4β2) (3x10-10 – 4.6x10-10 M - Rat), [3H]epibatidine (α4β2) (3x10-10 – 4.6x10-10 M - Rat), [3H]nicotine (α4β2) (4x10-10 M - Rat), [3H]cytisine (α4β2) (4.3x10-10 – 6.3x10-10 M), [125I]epibatidine (α4β4) (8.5x10-10 – 9.4x10-10 M - Rat), [3H]epibatidine (α4β4) (8.5x10-10 – 9.4x10-10 M - Rat) |
[125I]α-conotoxin MII, [3H]epibatidine (native α6β4*) (3.5x10-11 M - Chicken) |
[3H]epibatidine ((α7)5) (6x10-13 M), [3H]A-585539(native α7) (7x10-11 M) 202, [3H]AZ11637326((α7)5) (2.3x10-10 M) 216, [125I]α-bungarotoxin ((α7)5) (7x10-10 – 5x10-9 M), [3H]α-bungarotoxin ((α7)5) (7x10-10 – 5x10-9 M), [3H]methyllycaconitine (native α7*) (1.9x10-9 M - Rat) |
Functional characteristics |
α4β2: PCa/PNa = 1.65, Pf = 2.6 – 2.9%; α4β4: Pf = 1.5 – 3.0 % |
– |
PCa/PNa = 6.6-20, Pf = 8.8 - 11.4% |