Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameAlpha-2B adrenergic receptor    
Type of TargetClinical trial target    
Drug Potency against TargetEthyl-indol-1-yl-pyridin-4-yl-amineIC50 = 110 nM[1]
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinolineIC50 = 130 nM[2]
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amineIC50 = 2300 nM[1]
Indol-1-yl-methyl-pyridin-4-yl-amineIC50 = 24 nM[1]
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amineIC50 = 2500 nM[1]
Indol-1-yl-propyl-pyridin-4-yl-amineIC50 = 330 nM[1]
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amineIC50 = 3600 nM[1]
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amineIC50 = 500 nM[1]
Butyl-indol-1-yl-pyridin-4-yl-amineIC50 = 630 nM[1]
Indol-1-yl-pyridin-4-yl-amineIC50 = 8 nM[1]
RX-821002Ki = 0.36 nM[3]
MOXONIDINEKi = 1000 nM[4]
SNAP-5089Ki = 1088 nM[5]
A-80426Ki = 11 nM[6]
2,3,4,5-Tetrahydro-1H-benzo[c]azepineKi = 11000 nM[7]
GNF-PF-3878Ki = 1200 nM[9]
SK&F-104078;SK-104078Ki = 142 nM[10]
1',2',3',6'-Tetrahydro-[2,4']bipyridinylKi = 144 nM[11]
GNF-PF-3427Ki = 1500 nM[9]
C-Naphthalen-1-yl-methylamineKi = 1600 nM[12]
1,2,3,4,5,6-Hexahydro-benzo[c]azocineKi = 16000 nM[7]
2-Benzofuran-2-yl-4,5-dihydro-1H-imidazoleKi = 1900 nM[15]
WB-4101Ki = 200 nM[16]
SK&F-64139;SK-64139Ki = 21 nM[17]
5-Aminomethyl-naphthalen-2-olKi = 2100 nM[12]
1,2,3,4-Tetrahydro-isoquinolin-7-olKi = 2200 nM[12]
S-34324Ki = 23 nM[6]
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazoleKi = 24 nM[14]
(+/-)-nantenineKi = 252 nM[18]
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepineKi = 2600 nM[7]
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinolineKi = 2800 nM[19]
1,2,3,4-tetrahydroisoquinolineKi = 350 nM[17]
1-Pyridin-2-yl-piperazineKi = 37 nM[11]
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinolineKi = 3800 nM[20]
GNF-PF-2857Ki = 3800 nM[9]
TRAMAZOLINEKi = 4.2 nM[16]
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepineKi = 4100 nM[7]
SNAP-5150Ki = 420 nM[5]
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocyclohepteneKi = 4600 nM[7]
C-(6-Methoxy-naphthalen-1-yl)-methylamineKi = 4600 nM[12]
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazineKi = 5 nM[11]
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indoleKi = 516 nM[21]
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinolineKi = 520 nM[7]
INDORAMINKi = 528 nM[10]
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinolineKi = 6200 nM[7]
(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanolKi = 6600 nM[19]
4-Benzo[b]thiophen-4-yl-1H-imidazoleKi = 663 nM[22]
TRYPTOLINEKi = 710 nM[23]
TRACIZOLINEKi = 7413 nM[23]
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-olKi = 78 nM[12]
R-226161Ki = 8.4 nM[24]
4-(4-Methyl-indan-1-yl)-1H-imidazoleKi = 8.8 nM[25]
2,3-Dihydro-1H-isoindoleKi = 820 nM[7]
3-Methyl-1,2,3,4-tetrahydro-isoquinolineKi = 840 nM[7]
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinolineKi = 840 nM[12]
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carbolineKi = 8840 nM[23]
PIPEROXANKi = 95 nM[16]
Action against Disease ModelAGN-199981The compound involved is believed to be AgN-199981, an a2b-adrenergic agonist that was a highly potent and selective analgesic in animal models of neuropathic pain.[26]
The Effect of Target Knockout, Knockdown or Genetic VariationsAlpha 2A adrenergic receptor knockout mouse (alpha 2A-KO) showed an increase in sympathetic activity with resting tachycardia, depletion of cardiac tissue norepinephrine concentration. Knockout mouse study reveals that the alpha 2B adrenoceptor (alpha 2B AR) mediates the hypertensive response, and the alpha 2A AR mediates the hypotensive response, induced by alpha 2 agonists. Both the alpha 2A and alpha 2C AR subtypes are required for normal presynaptic control of transmitter release from sympathetic nerves. alpha 2A AR subtype inhibits transmitter release at high stimulation frequencies, whereas the alpha 2C AR subtype modulates neurotransmission at lower levels of nerve activity. Salt-induced hypertension experiment using alpha 2B-KO and alpha 2C-KO revealed that alpha 2B AR subtype is necessary to raise BP in response to dietary salt loading. Lack of adequately functional renal alpha 2B AR is thought to preclude reabsorption of sodi uM.[27]
Ref 1J Med Chem. 1996 Jan 19;39(2):570-81.Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeutic agents for Alzheimer's disease. To Reference
Ref 2J Med Chem. 1998 Oct 8;41(21):4165-70.N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies. To Reference
Ref 3J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. To Reference
Ref 4J Med Chem. 1996 Mar 15;39(6):1193-5.Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. To Reference
Ref 5Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists. To Reference
Ref 6J Med Chem. 2005 Mar 24;48(6):2054-71.Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking activity. To Reference
Ref 7J Med Chem. 1996 Aug 30;39(18):3539-46.Effect of ring size or an additional heteroatom on the potency and selectivity of bicyclic benzylamine-type inhibitors of phenylethanolamine N-methyltransferase. To Reference
Ref 8J Med Chem. 1986 Aug;29(8):1394-8.4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors. To Reference
Ref 9J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists. To Reference
Ref 10J Med Chem. 1995 Sep 1;38(18):3415-44.Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. To Reference
Ref 11J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. To Reference
Ref 12J Med Chem. 1997 Dec 5;40(25):3997-4005.Examination of the role of the acidic hydrogen in imparting selectivity of 7-(aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) toward inhibition of phenylethanolamine N-methyltransferase vs the alpha 2-adrenoceptor. To Reference
Ref 13J Med Chem. 1994 Apr 15;37(8):1060-2.A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. To Reference
Ref 14J Med Chem. 1994 Jul 22;37(15):2328-33.A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic receptors. To Reference
Ref 15Bioorg Med Chem Lett. 2000 Mar 20;10(6):605-7.Probes for imidazoline binding sites: synthesis and evaluation of a selective, irreversible I2 ligand. To Reference
Ref 16J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. To Reference
Ref 17J Med Chem. 2006 Sep 7;49(18):5424-33.Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase. To Reference
Ref 18Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. To Reference
Ref 19J Med Chem. 1999 Jun 3;42(11):1982-90.3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferase versus the alpha2-adrenoceptor. To Reference
Ref 20J Med Chem. 2005 Jan 13;48(1):134-40.3-hydroxymethyl-7-(N-substituted aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline inhibitors of phenylethanolamine N-methyltransferase that display remarkable potency and selectivity. To Reference
Ref 21Bioorg Med Chem Lett. 2004 Feb 23;14(4):1003-5.Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I(2) receptor ligands. To Reference
Ref 22J Med Chem. 2000 Mar 9;43(5):765-8.alpha(2) Adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene [corrected] as a high-affinity ligand for the alpha(2D) adrenergic receptor. To Reference
Ref 23Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors. To Reference
Ref 24Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. To Reference
Ref 25J Med Chem. 1997 Sep 12;40(19):3014-24.Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potential binding interactions with alpha 2-adrenoceptors involving a "methyl pocket". To Reference
Ref 26BioPartnering TODAY, Winter 2005/2006. To Reference
Ref 27Masui. 2001 Jan;50(1):12-9.Adrenergic receptor and knockout mouse: 2). Alpha adrenergic receptor knockout mouse. To Reference


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