Therapeutic Targets Database
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TTD Target ID: TTDS00032

Target Information
NameAlpha-2A adrenergic receptor    
Type of targetSuccessful target    
SynonymsAlpha-2A adrenoceptor    
Alpha-2A adrenoreceptor    
Alpha-2AAR subtype C10    
DiseaseHeart failure    [1]
Hypertension    [1]
Ischemic heart disease    [1]
Drug(s)BrimonidineApprovedOpen-angle glaucoma and ocular hypertension[2][3][4]
ConnexynApprovedAttention deficit hyperactivity disorder[5]
BioChemical ClassG-protein coupled receptor (rhodopsin family)    
PathwayNeuroactive ligand-receptor interaction
UniProt IDP08913
PDB Structure1HLL; 1HO9; 1HOD; 1HOF.    
FunctionAlpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine.    
SequenceMGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Target ValidationClick to Find Target Validation Information.    
Inhibitor (+/-)-nantenine[6]
(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol[7]
(1H-Benzoimidazol-5-yl)-[8]
(1H-Imidazol-2-yl)-quinoxalin-6-yl-amine[8]
(2,6-Dichloro-phenyl)-[8]
(2-Bromo-phenyl)-[8]
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine[9]
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine[9]
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine[9]
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline[10]
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline[10]
1',2',3',6'-Tetrahydro-[2,4']bipyridinyl[11]
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline[12]
1,2,3,4,5,6-Hexahydro-benzo[c]azocine[10]
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol[13]
1,2,3,4-Tetrahydro-isoquinolin-7-ol[13]
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole[14]
1,2,3,4-tetrahydroisoquinoline[15]
1- ([16]
1- (3-Fluoro-pyridin-2-yl)-4-methyl-piperazine[11]
1-Pyridin-2-yl-piperazine[11]
2,3,4,5-Tetrahydro-1H-benzo[c]azepine[10]
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine[10]
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine[10]
2,3-Dihydro-1H-isoindole[10]
2-Benzofuran-2-yl-4,5-dihydro-1H-imidazole[17]
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline[18]
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline[7]
3-Methyl-1,2,3,4-tetrahydro-isoquinoline[10]
3-Methyl-7-nitro-1,2,3,4-tetrahydro-isoquinoline[19]
4- (1-Naphthalen-1-yl-ethyl)-1H-imidazole[20]
4- (4-Methyl-indan-1-yl)-1H-imidazole[21]
4- (4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one[22]
4-Benzo[b]thiophen-4-yl-1H-imidazole[23]
5-Aminomethyl-naphthalen-2-ol[13]
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene[10]
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline[24]
7-Nitro-1,2,3,4-tetrahydro-isoquinoline[19]
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline[13]
A-80426[25]
AKUAMMIGINE[26]
AR-129330[27]
AR-129330[28]
ATC-0175[29]
BP-897[30]
Butyl-indol-1-yl-pyridin-4-yl-amine[9]
C- (6-Methoxy-naphthalen-1-yl)-methylamine[13]
C-Naphthalen-1-yl-methylamine[13]
Ethyl-indol-1-yl-pyridin-4-yl-amine[9]
GNF-PF-2857[31]
GNF-PF-3427[31]
GNF-PF-3878[31]
Indol-1-yl-methyl-pyridin-4-yl-amine[9]
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine[9]
Indol-1-yl-propyl-pyridin-4-yl-amine[9]
Indol-1-yl-pyridin-4-yl-amine[9]
MAZAPERTINE[32]
MEDETOMIDINE[20]
METHYLNORADRENALINE[33]
MEZILAMINE[34]
MOXONIDINE[35]
PIPEROXAN[33]
R-226161[36]
RX-821002[37]
S-34324[25]
SK&F-104078,   SK-104078[38]
SK&F-29661,   SK-29661[19]
SK&F-64139,   SK-64139[15]
SNAP-5089[39]
SNAP-5150[39]
TRACIZOLINE[24]
TRAMAZOLINE[33]
TRYPTOLINE[24]
WB-4101[33]
Yohimbine Hydrochloride[40]
Agonist4-Methoxyamphetamine[41]
Brimonidine[2][3][4]
Chloroethylclonidine[42]
Connexyn[5]
AntagonistBRL 44408[3][43]
Ciproxifan[44]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1The alpha2 -adrenergic receptors in hypertension and heart failure: experimental and clinical studies. J Hypertens. 2001 Dec;19(12):2115-24. To Reference
Ref 2alpha(2A)-adrenoceptor: G(alphai1) protein-mediated pertussis toxin-resistant attenuation of G(s) coupling to the cyclic AMP pathway. Biochem Pharmacol. 2000 Jun 15;59(12):1531-8. To Reference
Ref 3Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55. To Reference
Ref 4Decreased density of presynaptic alpha 2-adrenoceptors in postmortem brains of patients with Alzheimer's disease. J Neurochem. 1992 May;58(5):1896-904. To Reference
Ref 5alpha(2A)-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Jun 12. [Epub ahead of print] To Reference
Ref 6Bioorg 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 7J 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 8J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. To Reference
Ref 9J 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 10J 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 11J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. To Reference
Ref 12J 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 13J 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 14Bioorg 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 15J 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 16J Med Chem. 2006 Jan 12;49(1):318-28.1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. To Reference
Ref 17Bioorg 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 18J 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 19Bioorg Med Chem Lett. 2005 Feb 15;15(4):1143-7.Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines. To Reference
Ref 20J 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 21J 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 22J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 23J Med Chem. 2000 Apr 6;43(7):1423-6.Alpha(2) adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-imidazo)-1,3-dimethyl-6,7-dihydro-thianaphthene as a high-affinity ligand for the alpha(2D) adrenergic receptor. To Reference
Ref 24Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors. To Reference
Ref 25J 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 26J Med Chem. 1995 Sep 15;38(19):3681-716.Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. To Reference
Ref 27Bioorg Med Chem Lett. 2005 Sep 1;15(17):3853-6.Lead optimization of 4-(dimethylamino)quinazolines, potent and selective antagonists for the melanin-concentrating hormone receptor 1. To Reference
Ref 28Bioorg Med Chem Lett. 2005 May 16;15(10):2565-9.Discovery of 4-(dimethylamino)quinazolines as potent and selective antagonists for the melanin-concentrating hormone receptor 1. To Reference
Ref 29Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. Epub 2009 Sep 6.Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation. To Reference
Ref 30J Med Chem. 2003 Aug 28;46(18):3822-39.Synthesis and pharmacological evaluation of potent and highly selective D3 receptor ligands: inhibition of cocaine-seeking behavior and the role of dopamine D3/D2 receptors. To Reference
Ref 31J 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 32J 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 33J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. To Reference
Ref 34J Med Chem. 1986 Aug;29(8):1394-8.4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors. To Reference
Ref 35J 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 36Bioorg 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 37J 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 38J 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 39Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists. To Reference
Ref 40J Med Chem. 2009 Dec 10;52(23):7397-409.Further studies on arylpiperazinyl alkyl pyridazinones: discovery of an exceptionally potent, orally active, antinociceptive agent in thermally induced pain. To Reference
Ref 41Daws LC, Irvine RJ, Callaghan PD, Toop NP, White JM, Bochner F: Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Aug;24(6):955-77. To Reference
Ref 42Selective irreversible binding of chloroethylclonidine at alpha 1- and alpha 2-adrenoceptor subtypes. Mol Pharmacol. 1993 Dec;44(6):1165-70. To Reference
Ref 43Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1075-83. To Reference
Ref 44The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005 Feb;4(2):107-20. To Reference



 

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