Target Information

Target General Infomation
Target ID
T01777
Former ID
TTDR01180
Target Name
Alpha-2C adrenergic receptor
Gene Name
ADRA2C
Synonyms
Alpha-2C adrenoceptor; Alpha-2C adrenoreceptor; Subtype C4; ADRA2C
Target Type
Successful
Disease Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Alcohol use disorders [ICD9: 303; ICD10: F10.2]
Alzheimer disease [ICD9: 331; ICD10: G30]
Asthma [ICD10: J45]
Contusion [ICD10: S36.220S]
Depression [ICD9: 311; ICD10: F30-F39]
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Dementia; Obesity [ICD9:290-294, 278; ICD10: F01-F07, E66]
Diabetic nephropathy; Fibromyalgia [ICD9:250.4, 729.1; ICD10: E11.21, M79.7]
Erythema [ICD9: 695; ICD10: L51-L54]
Fibromyalgia [ICD9: 729.1; ICD10: M79.7]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Hypertension [ICD9: 401; ICD10: I10-I16]
Hypotension [ICD9: 458, 796.3; ICD10: I95]
Heart arrhythmia [ICD10: I47-I49]
Heart failure [ICD9: 428; ICD10: I50]
Male sexual disorders [ICD10: F52]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Ocular disease [ICD10: H00-H59]
Obesity [ICD9: 278; ICD10: E66]
Ocular hypertension [ICD9: 365.04; ICD10: H40.0]
Prostate disease [ICD10: N42.9]
Poison intoxication [ICD10: T36-T50]
Peptic ulcer [ICD9: 531-534; ICD10: K25-K27]
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.
BioChemical Class
GPCR rhodopsin
Target Validation
T01777
UniProt ID
P18825
Sequence
MASPALAAALAVAAAAGPNASGAGERGSGGVANASGASWGPPRGQYSAGAVAGLAAVVGF
LIVFTVVGNVLVVIAVLTSRALRAPQNLFLVSLASADILVATLVMPFSLANELMAYWYFG
QVWCGVYLALDVLFCTSSIVHLCAISLDRYWSVTQAVEYNLKRTPRRVKATIVAVWLISA
VISFPPLVSLYRQPDGAAYPQCGLNDETWYILSSCIGSFFAPCLIMGLVYARIYRVAKLR
TRTLSEKRAPVGPDGASPTTENGLGAAAGAGENGHCAPPPADVEPDESSAAAERRRRRGA
LRRGGRRRAGAEGGAGGADGQGAGPGAAESGALTASRSPGPGGRLSRASSRSVEFFLSRR
RRARSSVCRRKVAQAREKRFTFVLAVVMGVFVLCWFPFFFSYSLYGICREACQVPGPLFK
FFFWIGYCNSSLNPVIYTVFNQDFRRSFKHILFRRRRRGFRQ
Structure
1HLL; 1HO9; 1HOD; 1HOF
Drugs and Mode of Action
Drug(s) Amezinium Drug Info Approved Hypotension [1]
Amosulalol Drug Info Approved Hypertension [2]
Brimonidine Drug Info Approved Ocular hypertension [3], [4]
Dihydroergocristine Drug Info Approved Alcohol use disorders [5], [6]
MOXONIDINE Drug Info Approved Alcohol use disorders [7]
Propylhexedrine Drug Info Approved Obesity [1]
Rilmenidine Drug Info Approved Hypertension [1]
Tetrahydrozoline Drug Info Approved Ocular disease [8]
Xylometazoline Drug Info Phase 4 Allergic rhinitis [9], [10]
IDAZOXAN HYDROCHLORIDE Drug Info Phase 3 Neurological disease [11]
TNX-102 Drug Info Phase 3 Fibromyalgia [12]
AGN-XX/YY Drug Info Phase 2 Diabetic nephropathy; Fibromyalgia [13]
MEDETOMIDINE Drug Info Phase 2 Pain [14]
ORM-12741 Drug Info Phase 2 Alzheimer disease [15]
V-101 Drug Info Phase 2 Erythema [16]
INDORAMIN Drug Info Withdrawn from market Hypertension [17], [1]
Ecabapide Drug Info Discontinued in Preregistration Peptic ulcer [18]
Delequamine hydrochloride Drug Info Discontinued in Phase 3 Male sexual disorders [19]
FLUPAROXAN Drug Info Discontinued in Phase 3 Depression [20], [21]
NOLOMIROLE HYDROCHLORIDE Drug Info Discontinued in Phase 3 Heart failure [22]
Deriglidole Drug Info Discontinued in Phase 2 Diabetes [23]
Fadolmidine Drug Info Discontinued in Phase 2 Pain [24]
GYKI-16084 Drug Info Discontinued in Phase 2 Prostate disease [25]
JTH-601 Drug Info Discontinued in Phase 2 Prostate disease [26]
MAZAPERTINE Drug Info Discontinued in Phase 2 Discovery agent [27]
MK-912 Drug Info Discontinued in Phase 2 Discovery agent [28]
NMI-870 Drug Info Discontinued in Phase 2 Sexual dysfunction [29]
SGB-1534 Drug Info Discontinued in Phase 2 Hypotension [30]
GYKI-12743 Drug Info Discontinued in Phase 1 Hypertension [31]
A-75169 Drug Info Terminated Glaucoma [32]
A-80426 Drug Info Terminated Discovery agent [33]
ARC239 Drug Info Terminated Discovery agent [34], [35]
F-14413 Drug Info Terminated Alzheimer disease [36]
Midaglizole Drug Info Terminated Asthma [37]
SK&F-104078 Drug Info Terminated Discovery agent [38]
SNAP-5089 Drug Info Terminated Heart arrhythmia [39], [40]
WB-4101 Drug Info Terminated Discovery agent [41], [42]
Inhibitor (+/-)-nantenine Drug Info [43]
(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol Drug Info [44]
(1H-Benzoimidazol-5-yl)-(1H-imidazol-2-yl)-amine Drug Info [45]
(1H-Imidazol-2-yl)-quinoxalin-6-yl-amine Drug Info [45]
(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine Drug Info [45]
(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine Drug Info [45]
(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine Drug Info [46]
(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine Drug Info [46]
(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine Drug Info [46]
(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline Drug Info [47]
(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline Drug Info [47]
1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline Drug Info [48]
1,2,3,4,5,6-Hexahydro-benzo[c]azocine Drug Info [47]
1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol Drug Info [49]
1,2,3,4-Tetrahydro-isoquinolin-7-ol Drug Info [49]
1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole Drug Info [50]
1,2,3,4-tetrahydroisoquinoline Drug Info [51]
1-((S)-2-aminopropyl)-1H-indazol-6-ol Drug Info [52]
2,3,4,5-Tetrahydro-1H-benzo[c]azepine Drug Info [47]
2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine Drug Info [47]
2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine Drug Info [47]
2,3-Dihydro-1H-isoindole Drug Info [47]
2-BFi Drug Info [53]
3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline Drug Info [54]
3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline Drug Info [44]
3-Methyl-1,2,3,4-tetrahydro-isoquinoline Drug Info [47]
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole Drug Info [55]
4-(4-Methyl-indan-1-yl)-1H-imidazole Drug Info [56]
5-Aminomethyl-naphthalen-2-ol Drug Info [49]
6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene Drug Info [47]
7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline Drug Info [57]
8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline Drug Info [49]
A-80426 Drug Info [58]
Butyl-indol-1-yl-pyridin-4-yl-amine Drug Info [46]
C-(6-Methoxy-naphthalen-1-yl)-methylamine Drug Info [49]
C-Naphthalen-1-yl-methylamine Drug Info [49]
CONESSINE Drug Info [59]
Ethyl-indol-1-yl-pyridin-4-yl-amine Drug Info [46]
GNF-PF-2857 Drug Info [60]
GNF-PF-3427 Drug Info [60]
GNF-PF-3878 Drug Info [60]
Indol-1-yl-methyl-pyridin-4-yl-amine Drug Info [46]
Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine Drug Info [46]
Indol-1-yl-propyl-pyridin-4-yl-amine Drug Info [46]
Indol-1-yl-pyridin-4-yl-amine Drug Info [46]
INDORAMIN Drug Info [61]
MAZAPERTINE Drug Info [62]
MEDETOMIDINE Drug Info [55]
METHYLNORADRENALINE Drug Info [63]
MEZILAMINE Drug Info [64]
MOXONIDINE Drug Info [65]
PIPEROXAN Drug Info [63]
R-226161 Drug Info [66]
RX-821002 Drug Info [67]
S-34324 Drug Info [58]
SK&F-104078 Drug Info [61]
SK&F-64139 Drug Info [51]
SNAP-5089 Drug Info [68]
SNAP-5150 Drug Info [68]
TRACIZOLINE Drug Info [57]
TRAMAZOLINE Drug Info [63]
TRYPTOLINE Drug Info [57]
WB-4101 Drug Info [63]
Modulator (allosteric modulator) 5-(N,N-hexamethylene)-amiloride Drug Info [69]
Antagonist 5-methylurapidil Drug Info [70]
all-trans-4-oxo-retinoic acid Drug Info [71]
ARC239 Drug Info [72]
Ciproxifan Drug Info [73]
F-14413 Drug Info [74]
GYKI-16084 Drug Info [75]
JP1302 Drug Info [76]
JTH-601 Drug Info [77]
MK-912 Drug Info [78]
ORM-12741 Drug Info [79]
piribedil Drug Info [80]
spiroxatrine Drug Info [81]
TNX-102 Drug Info [82]
[125I]BE-2254 Drug Info [83]
[3H]MK-912 Drug Info [84]
[3H]rauwolscine Drug Info [85]
[3H]RX821002 Drug Info [86]
Agonist 6-fluoro-noradrenaline Drug Info [87]
A61603 Drug Info [88]
AGN-XX/YY Drug Info [89]
amidephrine Drug Info [87]
Chloroethylclonidine Drug Info [90]
cirazoline Drug Info [87]
Fadolmidine Drug Info [91]
indanidine Drug Info [87]
SKF 89748 Drug Info [87]
V-101 Drug Info [92]
xylazine Drug Info [93]
[125I]HEAT Drug Info [94]
Modulator A-75169 Drug Info [95]
Amezinium Drug Info [96], [1]
Amosulalol Drug Info [2], [1]
Brimonidine Drug Info [3]
Delequamine hydrochloride Drug Info [97]
Deriglidole Drug Info [98]
Dihydroergocristine Drug Info [5], [1]
Ecabapide Drug Info [99]
ETHOXY-IDAZOXAN Drug Info [100]
FLUPAROXAN Drug Info [101]
GYKI-12743 Drug Info [102]
IDAZOXAN HYDROCHLORIDE Drug Info [103]
Midaglizole Drug Info [104]
NMI-870 Drug Info [105]
NOLOMIROLE HYDROCHLORIDE Drug Info [106]
Propylhexedrine Drug Info [107], [1]
Rilmenidine Drug Info [108], [1]
SGB-1534 Drug Info [109]
Tetrahydrozoline Drug Info [8], [1]
V-103 Drug Info [110]
Xylometazoline Drug Info [111], [1]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway cGMP-PKG signaling pathway
Neuroactive ligand-receptor interaction
PANTHER Pathway Alpha adrenergic receptor signaling pathway
Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated 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 1Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 2Effects of amosulalol, a combined alpha 1- and beta-adrenoceptor-blocking agent, on ischemic myocardial energy metabolism in dogs. J Pharm Sci. 1993 Mar;82(3):291-5.
REF 3(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: 520).
REF 4ClinicalTrials.gov (NCT00675207) Comparison of Brimonidine Purite, Dorzolamide, and Brinzolamide as Adjunctive Therapy to Prostaglandin Analogs. U.S. National Institutes of Health.
REF 5Effect of dihydroergocristine on blood pressure and activity at peripheral alpha-adrenoceptors in pithed rats. Eur J Pharmacol. 1984 Jan 13;97(1-2):21-7.
REF 6(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: 278).
REF 7The 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 8Prolonged cardiovascular effects after unintentional ingestion of tetrahydrozoline. Clin Toxicol (Phila). 2008 Feb;46(2):171-2.
REF 9(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: 517).
REF 10ClinicalTrials.gov (NCT00630474) Nasal Decongestion and Obstructive Sleep Apnea. U.S. National Institutes of Health.
REF 11ClinicalTrials.gov (NCT00294944) The Effectiveness of Idazoxan in Treating TRD. U.S. National Institutes of Health.
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017946)
REF 13Clinical pipeline report, company report or official report of ACADIA Pharmaceuticals.
REF 14Sedative 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 15ClinicalTrials.gov (NCT02471196) Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Alzheimer's Disease.
REF 16ClinicalTrials.gov (NCT01186068) Dose Response Study of Patients With Erythematous Rosacea. U.S. National Institutes of Health.
REF 17(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: 501).
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000582)
REF 19Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008832)
REF 20(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: 41).
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000678)
REF 22Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003364)
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000010)
REF 24Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013220)
REF 25Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010746)
REF 26Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010685)
REF 27Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002662)
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000716)
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014166)
REF 30Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000148)
REF 31Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002059)
REF 32Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003469)
REF 33Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006017)
REF 34(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: 524).
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000266)
REF 36Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019997)
REF 37Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000085)
REF 38Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000354)
REF 39(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 40Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006771)
REF 41(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 42Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004048)
REF 43Bioorg 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 44J 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 45J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.
REF 46J 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 47J 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 48J Med Chem. 1998 Oct 8;41(21):4165-70.N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies.
REF 49J 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 50Bioorg 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 51J 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 52J 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 53Bioorg 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 54J 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 55J 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 56J 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 57Bioorg Med Chem Lett. 2004 Jan 19;14(2):527-9.Binding of an imidazopyridoindole at imidazoline I2 receptors.
REF 58J 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 59J Med Chem. 2008 Sep 11;51(17):5423-30. Epub 2008 Aug 7.The alkaloid conessine and analogues as potent histamine H3 receptor antagonists.
REF 60J Med Chem. 2006 Oct 19;49(21):6351-63.Structure-activity relationship of quinoline derivatives as potent and selective alpha(2C)-adrenoceptor antagonists.
REF 61J 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 62J 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 63J Med Chem. 1982 Dec;25(12):1389-401.alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs.
REF 64J Med Chem. 1986 Aug;29(8):1394-8.4-Amino-6-chloro-2-piperazinopyrimidines with selective affinity for alpha 2-adrenoceptors.
REF 65J 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 66Bioorg 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 67J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists.
REF 68Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.Design and synthesis of novel dihydropyridine alpha-1a antagonists.
REF 69Characterization of the allosteric interactions between antagonists and amiloride analogues at the human alpha2A-adrenergic receptor. Mol Pharmacol. 1998 May;53(5):916-25.
REF 70Phe-308 and Phe-312 in transmembrane domain 7 are major sites of alpha 1-adrenergic receptor antagonist binding. Imidazoline agonists bind like antagonists. J Biol Chem. 2001 Jul 6;276(27):25366-71. Epub 2001 Apr 30.
REF 71Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12.
REF 72Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55.
REF 73The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005 Feb;4(2):107-20.
REF 74Activation of noradrenergic transmission by alpha2-adrenoceptor antagonists counteracts deafferentation-induced neuronal death and cell proliferation in the adult mouse olfactory bulb. Exp Neurol. 2005 Aug;194(2):444-56.
REF 75A novel approach to the treatment of benign prostatic hyperplasia. BJU Int. 2006 Jun;97(6):1252-5.
REF 76Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302. Br J Pharmacol. 2007 Feb;150(4):391-402. Epub 2007 Jan 15.
REF 77Effect of JTH-601, a novel alpha(1)-adrenoceptor antagonist, on prostate function in dogs. Eur J Pharmacol. 2000 Apr 7;394(1):123-30.
REF 78Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries. Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1075-83.
REF 79A double-blind, randomized, placebo-controlled crossover trial of the alpha2C-adrenoceptor antagonist ORM-12741 for prevention of cold-induced vasospasm in patients with systemic sclerosis. Rheumatology (Oxford). 2014 May;53(5):948-52.
REF 80Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002 Nov;303(2):791-804.
REF 81Affinity of serotonin receptor antagonists and agonists to recombinant and native alpha1-adrenoceptor subtypes. Jpn J Pharmacol. 2001 Jun;86(2):189-95.
REF 82Clinical pipeline report, company report or official report of Tonix Pharmaceuticals.
REF 83Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J Pharmacol Exp Ther. 1995 Jan;272(1):134-42.
REF 84The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. J Pharmacol Exp Ther. 1994 Dec;271(3):1558-65.
REF 85Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol. 1992 Jul;42(1):1-5.
REF 86Further characterization of human alpha 2-adrenoceptor subtypes: [3H]RX821002 binding and definition of additional selective drugs. Eur J Pharmacol. 1994 Jan 24;252(1):43-9.
REF 87Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes. Mol Pharmacol. 1994 Nov;46(5):929-36.
REF 88A-61603, a potent alpha 1-adrenergic receptor agonist, selective for the alpha 1A receptor subtype. J Pharmacol Exp Ther. 1995 Jul;274(1):97-103.
REF 89Patent WO2008058220 A2.
REF 90Selective irreversible binding of chloroethylclonidine at alpha 1- and alpha 2-adrenoceptor subtypes. Mol Pharmacol. 1993 Dec;44(6):1165-70.
REF 91Antinociceptive properties of fadolmidine (MPV-2426), a novel alpha2-adrenoceptor agonist. CNS Drug Rev. 2004 Summer;10(2):117-26.
REF 92Rosacea: update on management and emerging therapies. Skin Therapy Lett. 2012 Dec;17(10):1-4.
REF 93Ligand efficacy and potency at recombinant alpha2 adrenergic receptors: agonist-mediated [35S]GTPgammaS binding. Biochem Pharmacol. 1998 Apr 1;55(7):1035-43.
REF 94KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues. Mol Pharmacol. 1995 Aug;48(2):250-8.
REF 95A-75169 HCI: Pharmacological profile and ocular pharmacology studies of a new alpha-2 antagonist. Drug Development Research Volume 28, Issue 1, pages 56-64, January 1993.
REF 96Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforschung. 1981;31(9a):1558-65.
REF 97Modulation of sexual behaviour in the rat by a potent and selective alpha 2-adrenoceptor antagonist, delequamine (RS-15385-197). Br J Pharmacol. 1996 May;118(1):63-72.
REF 98Mechanisms of the hypoglycemic effects of the alpha2-adrenoceptor antagonists SL84.0418 and deriglidole. Life Sci. 1998;62(9):839-52.
REF 99Identification of major biliary and urinary metabolites of ecabapide in rats. Xenobiotica. 1996 Sep;26(9):983-94.
REF 100Discriminative stimulus properties of ethoxy idazoxan. J Psychopharmacol. 1995 Jan;9(3):228-33.
REF 101The pharmacology of fluparoxan: a selective alpha 2-adrenoceptor antagonist. Br J Pharmacol. 1991 Apr;102(4):887-95.
REF 102GYKI-12743 a new postsynaptic vascular alpha-adrenoceptor antagonist. Acta Physiol Hung. 1991;77(3-4):257-67.
REF 103Different sites of action for alpha 2-adrenoceptor antagonists in the modulation of noradrenaline release and contraction response in the vas deferens of the rat. J Pharm Pharmacol. 1992 Mar;44(3):231-4.
REF 104Studies of midaglizole (DG-5128). A new type of oral hypoglycemic drug in healthy subjects. Diabetes. 1987 Feb;36(2):216-20.
REF 105Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269.
REF 106Effect of nolomirole on monocrotaline-induced heart failure. Pharmacol Res. 2004 Jan;49(1):1-5.
REF 107Airway compromise and delayed death following attempted central vein injection of propylhexedrine. J Emerg Med. 1994 Nov-Dec;12(6):795-7.
REF 108Rilmenidine-induced ocular hypotension: role of imidazoline1 and alpha 2 receptors. Curr Eye Res. 1996 Sep;15(9):943-50.
REF 109Potent alpha-adrenoceptor blocking action of SGB-1534, a new quinazoline antihypertensive agent in vitro experiments. Gen Pharmacol. 1986;17(2):143-9.
REF 110(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. (Target id: 27).
REF 111Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.