Target Information
Target General Infomation | |||||
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Target ID |
T11448
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Former ID |
TTDS00032
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Target Name |
Alpha-2A adrenergic receptor
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Gene Name |
ADRA2A
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Synonyms |
Alpha-2A adrenoceptor; Alpha-2A adrenoreceptor; Alpha-2AAR subtype C10; ADRA2A
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Target Type |
Successful
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Disease | Alcohol use disorders [ICD9: 303; ICD10: F10.2] | ||||
Attention deficit hyperactivity disorder [ICD9: 314; ICD10: F90] | |||||
Dementia; Obesity [ICD9:290-294, 278; ICD10: F01-F07, E66] | |||||
Heart arrhythmia [ICD10: I47-I49] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Sexual dysfunction [ICD9: 302.7; ICD10: F52] | |||||
Function |
Alpha-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 > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone= prazosin > propanolol > alprenolol = pindolol.
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BioChemical Class |
GPCR rhodopsin
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Target Validation |
T11448
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UniProt ID | |||||
Sequence |
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS LNPVIYTIFNHDFRRAFKKILCRGDRKRIV |
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Drugs and Mode of Action | |||||
Drug(s) | Connexyn | Drug Info | Approved | Attention deficit hyperactivity disorder | [550610] |
MOXONIDINE | Drug Info | Approved | Alcohol use disorders | [526626] | |
MEDETOMIDINE | Drug Info | Phase 2 | Pain | [529347] | |
MAZAPERTINE | Drug Info | Discontinued in Phase 2 | Discovery agent | [545274] | |
NMI-870 | Drug Info | Discontinued in Phase 2 | Sexual dysfunction | [547220] | |
A-80426 | Drug Info | Terminated | Discovery agent | [546043] | |
S-18616 | Drug Info | Terminated | Pain | [546405] | |
SK&F-104078 | Drug Info | Terminated | Discovery agent | [544626] | |
SNAP-5089 | Drug Info | Terminated | Heart arrhythmia | [468115], [546179] | |
WB-4101 | Drug Info | Terminated | Discovery agent | [468117], [545656] | |
Inhibitor | (+/-)-nantenine | Drug Info | [530558] | ||
(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol | Drug Info | [525507] | |||
(1H-Benzoimidazol-5-yl)-(1H-imidazol-2-yl)-amine | Drug Info | [534315] | |||
(1H-Imidazol-2-yl)-quinoxalin-6-yl-amine | Drug Info | [534315] | |||
(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine | Drug Info | [534315] | |||
(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine | Drug Info | [534315] | |||
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [534195] | |||
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [534195] | |||
1',2',3',6'-Tetrahydro-[2,4']bipyridinyl | Drug Info | [533509] | |||
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline | Drug Info | [534719] | |||
1,2,3,4,5,6-Hexahydro-benzo[c]azocine | Drug Info | [534195] | |||
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol | Drug Info | [534531] | |||
1,2,3,4-Tetrahydro-isoquinolin-7-ol | Drug Info | [534531] | |||
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole | Drug Info | [526994] | |||
1,2,3,4-tetrahydroisoquinoline | Drug Info | [528403] | |||
1-((S)-2-aminopropyl)-1H-indazol-6-ol | Drug Info | [527952] | |||
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine | Drug Info | [533509] | |||
1-(pyridin-2-yl)piperazine | Drug Info | [533509] | |||
2,3,4,5-Tetrahydro-1H-benzo[c]azepine | Drug Info | [534195] | |||
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine | Drug Info | [534195] | |||
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine | Drug Info | [534195] | |||
2,3-Dihydro-1H-isoindole | Drug Info | [534195] | |||
2-BFi | Drug Info | [525733] | |||
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [527365] | |||
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [525507] | |||
3-Methyl-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [534195] | |||
3-Methyl-7-nitro-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [527414] | |||
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole | Drug Info | [533805] | |||
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [531079] | |||
4-(4-Methyl-indan-1-yl)-1H-imidazole | Drug Info | [534467] | |||
4-Benzo[b]thiophen-4-yl-1H-imidazole | Drug Info | [525740] | |||
5-Aminomethyl-naphthalen-2-ol | Drug Info | [534531] | |||
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene | Drug Info | [534195] | |||
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline | Drug Info | [526918] | |||
7-Nitro-1,2,3,4-tetrahydro-isoquinoline | Drug Info | [527414] | |||
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline | Drug Info | [534531] | |||
A-80426 | Drug Info | [527481] | |||
AKUAMMIGINE | Drug Info | [533638] | |||
AR-129330 | Drug Info | [527629] | |||
Butyl-indol-1-yl-pyridin-4-yl-amine | Drug Info | [534087] | |||
C-(6-Methoxy-naphthalen-1-yl)-methylamine | Drug Info | [534531] | |||
C-Naphthalen-1-yl-methylamine | Drug Info | [534531] | |||
Ethyl-indol-1-yl-pyridin-4-yl-amine | Drug Info | [534087] | |||
GNF-PF-2857 | Drug Info | [528472] | |||
GNF-PF-3427 | Drug Info | [528472] | |||
GNF-PF-3878 | Drug Info | [528472] | |||
Indol-1-yl-methyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
Indol-1-yl-propyl-pyridin-4-yl-amine | Drug Info | [534087] | |||
Indol-1-yl-pyridin-4-yl-amine | Drug Info | [534087] | |||
MAZAPERTINE | Drug Info | [533800] | |||
MEDETOMIDINE | Drug Info | [533805] | |||
METHYLNORADRENALINE | Drug Info | [533545] | |||
MEZILAMINE | Drug Info | [533406] | |||
MOXONIDINE | Drug Info | [534128] | |||
PIPEROXAN | Drug Info | [533545] | |||
R-226161 | Drug Info | [528772] | |||
RX-821002 | Drug Info | [533375] | |||
S-34324 | Drug Info | [527481] | |||
SK&F-104078 | Drug Info | [533682] | |||
SK&F-29661 | Drug Info | [527414] | |||
SK&F-64139 | Drug Info | [528403] | |||
SNAP-5089 | Drug Info | [525611] | |||
SNAP-5150 | Drug Info | [525611] | |||
TRACIZOLINE | Drug Info | [526918] | |||
TRAMAZOLINE | Drug Info | [533545] | |||
TRYPTOLINE | Drug Info | [526918] | |||
WB-4101 | Drug Info | [533545] | |||
Agonist | 4-Methoxyamphetamine | Drug Info | [551380] | ||
Chloroethylclonidine | Drug Info | [537921] | |||
Connexyn | Drug Info | [537472] | |||
Antagonist | BRL 44408 | Drug Info | [534977], [535225] | ||
Ciproxifan | Drug Info | [536039] | |||
Modulator | NMI-870 | Drug Info | [544155] | ||
S-18616 | Drug Info | [525915] | |||
Pathways | |||||
KEGG Pathway | cGMP-PKG signaling pathway | ||||
Neuroactive ligand-receptor interaction | |||||
PANTHER Pathway | Alpha adrenergic receptor signaling pathway | ||||
Reactome | Adrenoceptors | ||||
Adrenaline signalling through Alpha-2 adrenergic receptor | |||||
Adrenaline,noradrenaline inhibits insulin secretion | |||||
G alpha (i) signalling events | |||||
G alpha (z) signalling events | |||||
Surfactant metabolism | |||||
WikiPathways | Monoamine GPCRs | ||||
GPCRs, Class A Rhodopsin-like | |||||
Platelet Aggregation (Plug Formation) | |||||
Integration of energy metabolism | |||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
Ref 468115 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 498). | ||||
Ref 468117 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 499). | ||||
Ref 526626 | The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat model of metabolic syndrome X. J Pharmacol Exp Ther.2003 Aug;306(2):646-57. Epub 2003 May 19. | ||||
Ref 529347 | Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves. Am J Vet Res. 2008 Mar;69(3):319-29. | ||||
Ref 544626 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000354) | ||||
Ref 545274 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002662) | ||||
Ref 545656 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004048) | ||||
Ref 546043 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006017) | ||||
Ref 546179 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006771) | ||||
Ref 546405 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007941) | ||||
Ref 525507 | J 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. | ||||
Ref 525611 | Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists. | ||||
Ref 525733 | Bioorg Med Chem Lett. 2000 Mar 20;10(6):605-7.Probes for imidazoline binding sites: synthesis and evaluation of a selective, irreversible I2 ligand. | ||||
Ref 525740 | J 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. | ||||
Ref 525915 | S18616, a highly potent spiroimidazoline agonist at alpha(2)-adrenoceptors: II. Influence on monoaminergic transmission, motor function, and anxiety in comparison with dexmedetomidine and clonidine. J Pharmacol Exp Ther. 2000 Dec;295(3):1206-22. | ||||
Ref 526918 | Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors. | ||||
Ref 526994 | Bioorg 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. | ||||
Ref 527365 | J 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. | ||||
Ref 527414 | Bioorg 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. | ||||
Ref 527481 | J 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. | ||||
Ref 527629 | Bioorg 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. | ||||
Ref 527952 | J 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. | ||||
Ref 528403 | J 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 phenylethanolamineN-methyltransferase. | ||||
Ref 528472 | J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists. | ||||
Ref 528772 | Bioorg 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. | ||||
Ref 530558 | Bioorg 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. | ||||
Ref 531079 | J 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. | ||||
Ref 533375 | J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. | ||||
Ref 533406 | J Med Chem. 1986 Aug;29(8):1394-8.4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors. | ||||
Ref 533509 | J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. | ||||
Ref 533545 | J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. | ||||
Ref 533638 | J 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. | ||||
Ref 533682 | J 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. | ||||
Ref 533800 | J 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. | ||||
Ref 533805 | J 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. | ||||
Ref 534087 | J 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. | ||||
Ref 534128 | J 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. | ||||
Ref 534195 | J 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. | ||||
Ref 534315 | J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. | ||||
Ref 534467 | J 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". | ||||
Ref 534531 | J 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. | ||||
Ref 534719 | J Med Chem. 1998 Oct 8;41(21):4165-70.N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies. | ||||
Ref 534977 | Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1075-83. | ||||
Ref 535225 | Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55. | ||||
Ref 536039 | The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005 Feb;4(2):107-20. | ||||
Ref 537472 | Alpha(2A)-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Jun 12. | ||||
Ref 537921 | Selective irreversible binding of chloroethylclonidine at alpha 1- and alpha 2-adrenoceptor subtypes. Mol Pharmacol. 1993 Dec;44(6):1165-70. |
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