Target Information

Target General Information

Target ID

T01777 (Former ID: TTDR01180)

Target Name

Adrenergic receptor alpha-2C (ADRA2C)

Synonyms

Subtype C4; Alpha-2CAR; Alpha-2C adrenoreceptor; Alpha-2C adrenoceptor; Alpha-2C adrenergic receptor; Alpha-2 adrenergic receptor subtype C4; ADRA2RL2; ADRA2L2

Gene Name

ADRA2C

Target Type

Successful target

[1]

Disease

[+] 6 Target-related Diseases

Glaucoma [ICD-11: 9C61]

Herpes simplex infection [ICD-11: 1F00]

Hypertension [ICD-11: BA00-BA04]

Hypotension [ICD-11: BA20-BA21]

Obesity [ICD-11: 5B80-5B81]

Substance abuse [ICD-11: 6C40]

Function

Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.

Click to Show/Hide

BioChemical Class

GPCR rhodopsin

UniProt ID

ADA2C_HUMAN

Sequence

MASPALAAALAVAAAAGPNASGAGERGSGGVANASGASWGPPRGQYSAGAVAGLAAVVGF
LIVFTVVGNVLVVIAVLTSRALRAPQNLFLVSLASADILVATLVMPFSLANELMAYWYFG
QVWCGVYLALDVLFCTSSIVHLCAISLDRYWSVTQAVEYNLKRTPRRVKATIVAVWLISA
VISFPPLVSLYRQPDGAAYPQCGLNDETWYILSSCIGSFFAPCLIMGLVYARIYRVAKLR
TRTLSEKRAPVGPDGASPTTENGLGAAAGAGENGHCAPPPADVEPDESSAAAERRRRRGA
LRRGGRRRAGAEGGAGGADGQGAGPGAAESGALTASRSPGPGGRLSRASSRSVEFFLSRR
RRARSSVCRRKVAQAREKRFTFVLAVVMGVFVLCWFPFFFSYSLYGICREACQVPGPLFK
FFFWIGYCNSSLNPVIYTVFNQDFRRSFKHILFRRRRRGFRQ

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 9 Approved Drugs

Amezinium

Drug Info

Approved

Hypotension

[2]

Amosulalol

Drug Info

Approved

Hypertension

[1]

Brimonidine

Drug Info

Approved

Ocular hypertension

[3], [4]

Dihydroergocristine

Drug Info

Approved

Alcohol dependence

[5], [6]

MOXONIDINE

Drug Info

Approved

Alcohol dependence

[7]

Propylhexedrine

Drug Info

Approved

Obesity

[2]

Rilmenidine

Drug Info

Approved

Hypertension

[2]

Tetrahydrozoline

Drug Info

Approved

Ocular disease

[8]

Xylometazoline

Drug Info

Phase 4

Allergic rhinitis

[9], [10]

Clinical Trial Drug(s)

[+] 8 Clinical Trial Drugs

IDAZOXAN HYDROCHLORIDE

Drug Info

Phase 3

Neurological disorder

[11]

TNX-102

Drug Info

Phase 3

Fibromyalgia

[12]

AGN-XX/YY

Drug Info

Phase 2

Fibromyalgia

[13]

BAY1193397

Drug Info

Phase 2

Peripheral arterial disease

[14]

Fadolmidine

Drug Info

Phase 2

Neuropathic pain

[15]

MEDETOMIDINE

Drug Info

Phase 2

Pain

[16]

ORM-12741

Drug Info

Phase 2

Alzheimer disease

[17]

V-101

Drug Info

Phase 2

Erythema

[18]

Discontinued Drug(s)

[+] 15 Discontinued Drugs

INDORAMIN

Drug Info

Withdrawn from market

Hypertension

[2], [19]

Ecabapide

Drug Info

Discontinued in Preregistration

Peptic ulcer

[20]

Delequamine hydrochloride

Drug Info

Discontinued in Phase 3

Male sexual disorder

[21]

FLUPAROXAN

Drug Info

Discontinued in Phase 3

Depression

[22], [23]

NOLOMIROLE HYDROCHLORIDE

Drug Info

Discontinued in Phase 3

Heart failure

[24]

Deriglidole

Drug Info

Discontinued in Phase 2

Diabetic complication

[25]

GYKI-16084

Drug Info

Discontinued in Phase 2

Prostate disease

[26]

JTH-601

Drug Info

Discontinued in Phase 2

Prostate disease

[27]

NMI-870

Drug Info

Discontinued in Phase 2

Sexual dysfunction

[28]

SGB-1534

Drug Info

Discontinued in Phase 2

Hypotension

[29]

GYKI-12743

Drug Info

Discontinued in Phase 1

Hypertension

[30]

A-75169

Drug Info

Terminated

Glaucoma/ocular hypertension

[32]

F-14413

Drug Info

Terminated

Alzheimer disease

[33]

Midaglizole

Drug Info

Terminated

Asthma

[34]

SNAP-5089

Drug Info

Terminated

Heart arrhythmia

[35], [36]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

5-(N,N-hexamethylene)-amiloride

Drug Info

Preclinical

Coronavirus infection

[31]

Mode of Action

[+] 5 Modes of Action

Modulator

[+] 21 Modulator drugs

Amezinium

Drug Info

[2], [37]

Amosulalol

Drug Info

[1], [2]

Brimonidine

Drug Info

[3]

Dihydroergocristine

Drug Info

[2], [6]

Propylhexedrine

Drug Info

[2], [39]

Rilmenidine

Drug Info

[2], [40]

Tetrahydrozoline

Drug Info

[2], [8]

Xylometazoline

Drug Info

[2], [41]

IDAZOXAN HYDROCHLORIDE

Drug Info

[42]

Ecabapide

Drug Info

[50]

Delequamine hydrochloride

Drug Info

[51]

FLUPAROXAN

Drug Info

[52]

NOLOMIROLE HYDROCHLORIDE

Drug Info

[53]

Deriglidole

Drug Info

[54]

NMI-870

Drug Info

[59]

SGB-1534

Drug Info

[60]

GYKI-12743

Drug Info

[61]

A-75169

Drug Info

[63]

Midaglizole

Drug Info

[67]

ETHOXY-IDAZOXAN

Drug Info

[91]

V-103

Drug Info

[98]

Inhibitor

[+] 60 Inhibitor drugs

MOXONIDINE

Drug Info

[38]

MEDETOMIDINE

Drug Info

[46]

INDORAMIN

Drug Info

[49]

MAZAPERTINE

Drug Info

[57]

A-80426

Drug Info

[64]

SK&F-104078

Drug Info

[49]

SNAP-5089

Drug Info

[68]

WB-4101

Drug Info

[69]

(+/-)-nantenine

Drug Info

[70]

(1,2,3,4-Tetrahydro-isoquinolin-3-yl)-methanol

Drug Info

[71]

(1H-Benzoimidazol-5-yl)-(1H-imidazol-2-yl)-amine

Drug Info

[72]

(1H-Imidazol-2-yl)-quinoxalin-6-yl-amine

Drug Info

[72]

(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine

Drug Info

[72]

(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine

Drug Info

[72]

(2-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine

Drug Info

[73]

(3-Ethyl-indol-1-yl)-propyl-pyridin-4-yl-amine

Drug Info

[73]

(3-Methyl-indol-1-yl)-propyl-pyridin-4-yl-amine

Drug Info

[73]

(R)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[74]

(S)-3-Methyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[74]

1,2,3,4,4a,5,10,10a-Octahydro-benzo[g]quinoline

Drug Info

[75]

1,2,3,4,5,6-Hexahydro-benzo[c]azocine

Drug Info

[74]

1,2,3,4-Tetrahydro-benzo[h]isoquinolin-8-ol

Drug Info

[76]

1,2,3,4-Tetrahydro-isoquinolin-7-ol

Drug Info

[76]

1,2,3,4-Tetrahydro-pyrazino[1,2-a]indole

Drug Info

[77]

1,2,3,4-tetrahydroisoquinoline

Drug Info

[78]

1-((S)-2-aminopropyl)-1H-indazol-6-ol

Drug Info

[79]

2,3,4,5-Tetrahydro-1H-benzo[c]azepine

Drug Info

[74]

2,3,4,5-Tetrahydro-1H-benzo[e][1,4]diazepine

Drug Info

[74]

2,3,4,5-Tetrahydro-benzo[f][1,4]oxazepine

Drug Info

[74]

2,3-Dihydro-1H-isoindole

Drug Info

[74]

2-BFi

Drug Info

[80]

3-Fluoromethyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[81]

3-Methoxymethyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[71]

3-Methyl-1,2,3,4-tetrahydro-isoquinoline

Drug Info

[74]

4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole

Drug Info

[46]

4-(4-Methyl-indan-1-yl)-1H-imidazole

Drug Info

[82]

5-Aminomethyl-naphthalen-2-ol

Drug Info

[76]

6,7,8,9-Tetrahydro-5-thia-8-aza-benzocycloheptene

Drug Info

[74]

7-Methoxy-2,3,4,9-tetrahydro-1H-beta-carboline

Drug Info

[85]

8-Methoxy-1,2,3,4-tetrahydro-benzo[h]isoquinoline

Drug Info

[76]

Butyl-indol-1-yl-pyridin-4-yl-amine

Drug Info

[73]

C-(6-Methoxy-naphthalen-1-yl)-methylamine

Drug Info

[76]

C-Naphthalen-1-yl-methylamine

Drug Info

[76]

CONESSINE

Drug Info

[90]

Ethyl-indol-1-yl-pyridin-4-yl-amine

Drug Info

[73]

GNF-PF-2857

Drug Info

[92]

GNF-PF-3878

Drug Info

[92]

Indol-1-yl-methyl-pyridin-4-yl-amine

Drug Info

[73]

Indol-1-yl-prop-2-ynyl-pyridin-4-yl-amine

Drug Info

[73]

Indol-1-yl-pyridin-4-yl-amine

Drug Info

[73]

METHYLNORADRENALINE

Drug Info

[69]

MEZILAMINE

Drug Info

[94]

PIPEROXAN

Drug Info

[69]

R-226161

Drug Info

[96]

S-34324

Drug Info

[64]

SK&F-64139

Drug Info

[78]

SNAP-5150

Drug Info

[68]

TRACIZOLINE

Drug Info

[85]

Tramazoline

Drug Info

[69]

TRYPTOLINE

Drug Info

[85]

Antagonist

[+] 18 Antagonist drugs

TNX-102

Drug Info

[43]

BAY1193397

Drug Info

[14]

ORM-12741

Drug Info

[47]

GYKI-16084

Drug Info

[55]

JTH-601

Drug Info

[56]

MK-912

Drug Info

[58]

ARC239

Drug Info

[65]

F-14413

Drug Info

[66]

5-methylurapidil

Drug Info

[83]

all-trans-4-oxo-retinoic acid

Drug Info

[87]

Ciproxifan

Drug Info

[89]

JP1302

Drug Info

[92], [93]

piribedil

Drug Info

[95]

spiroxatrine

Drug Info

[97]

[125I]BE-2254

Drug Info

[100]

[3H]MK-912

Drug Info

[102]

[3H]rauwolscine

Drug Info

[103]

[3H]RX821002

Drug Info

[104], [105]

Agonist

[+] 12 Agonist drugs

AGN-XX/YY

Drug Info

[44]

Fadolmidine

Drug Info

[45]

V-101

Drug Info

[48]

6-fluoro-noradrenaline

Drug Info

[84]

A61603

Drug Info

[86]

amidephrine

Drug Info

[84]

Chloroethylclonidine

Drug Info

[88]

cirazoline

Drug Info

[84]

indanidine

Drug Info

[84]

SKF 89748

Drug Info

[84]

xylazine

Drug Info

[99]

[125I]HEAT

Drug Info

[101]

Modulator (allosteric modulator)

[+] 1 Modulator (allosteric modulator) drugs

5-(N,N-hexamethylene)-amiloride

Drug Info

[62]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 2 KEGG Pathways

cGMP-PKG signaling pathway

Neuroactive ligand-receptor interaction

Panther Pathway

[+] 2 Panther Pathways

Alpha adrenergic receptor signaling pathway

Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway

Reactome

[+] 6 Reactome Pathways

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

[+] 6 WikiPathways

Monoamine GPCRs

GPCRs, Class A Rhodopsin-like

Platelet Aggregation (Plug Formation)

Integration of energy metabolism

GPCR ligand binding

GPCR downstream signaling

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

References

Top

REF 1

Effects 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 2

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 3

URL: 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 4

ClinicalTrials.gov (NCT00675207) Comparison of Brimonidine Purite, Dorzolamide, and Brinzolamide as Adjunctive Therapy to Prostaglandin Analogs. U.S. National Institutes of Health.

REF 5

REF 6

Effect 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 7

The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat ... J Pharmacol Exp Ther. 2003 Aug;306(2):646-57.

REF 8

Prolonged cardiovascular effects after unintentional ingestion of tetrahydrozoline. Clin Toxicol (Phila). 2008 Feb;46(2):171-2.

REF 9

REF 10

ClinicalTrials.gov (NCT00630474) Nasal Decongestion and Obstructive Sleep Apnea. U.S. National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT00294944) The Effectiveness of Idazoxan in Treating TRD. U.S. National Institutes of Health.

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017946)

REF 13

Clinical pipeline report, company report or official report of ACADIA Pharmaceuticals.

REF 14

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 15

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 16

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 17

ClinicalTrials.gov (NCT02471196) Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Alzheimer's Disease.

REF 18

ClinicalTrials.gov (NCT01186068) Dose Response Study of Patients With Erythematous Rosacea. U.S. National Institutes of Health.

REF 19

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000582)

REF 21

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008832)

REF 22

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000678)

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003364)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000010)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010746)

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010685)

REF 28

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014166)

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000148)

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002059)

REF 31

Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003469)

REF 33

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019997)

REF 34

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000085)

REF 35

REF 36

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 37

Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforschung. 1981;31(9a):1558-65.

REF 38

Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.

REF 39

Airway compromise and delayed death following attempted central vein injection of propylhexedrine. J Emerg Med. 1994 Nov-Dec;12(6):795-7.

REF 40

Rilmenidine-induced ocular hypotension: role of imidazoline1 and alpha 2 receptors. Curr Eye Res. 1996 Sep;15(9):943-50.

REF 41

Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.

REF 42

Different 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 43

Clinical pipeline report, company report or official report of Tonix Pharmaceuticals.

REF 44

Patent WO2008058220 A2.

REF 45

Antinociceptive properties of fadolmidine (MPV-2426), a novel alpha2-adrenoceptor agonist. CNS Drug Rev. 2004 Summer;10(2):117-26.

REF 46

A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.

REF 47

A 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 48

Rosacea: update on management and emerging therapies. Skin Therapy Lett. 2012 Dec;17(10):1-4.

REF 49

Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. J Med Chem. 1995 Sep 1;38(18):3415-44.

REF 50

Identification of major biliary and urinary metabolites of ecabapide in rats. Xenobiotica. 1996 Sep;26(9):983-94.

REF 51

Modulation 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 52

The pharmacology of fluparoxan: a selective alpha 2-adrenoceptor antagonist. Br J Pharmacol. 1991 Apr;102(4):887-95.

REF 53

Effect of nolomirole on monocrotaline-induced heart failure. Pharmacol Res. 2004 Jan;49(1):1-5.

REF 54

Mechanisms of the hypoglycemic effects of the alpha2-adrenoceptor antagonists SL84.0418 and deriglidole. Life Sci. 1998;62(9):839-52.

REF 55

A novel approach to the treatment of benign prostatic hyperplasia. BJU Int. 2006 Jun;97(6):1252-5.

REF 56

Effect 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 57

A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2.

REF 58

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 59

Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269.

REF 60

Potent alpha-adrenoceptor blocking action of SGB-1534, a new quinazoline antihypertensive agent in vitro experiments. Gen Pharmacol. 1986;17(2):143-9.

REF 61

GYKI-12743 a new postsynaptic vascular alpha-adrenoceptor antagonist. Acta Physiol Hung. 1991;77(3-4):257-67.

REF 62

Characterization of the allosteric interactions between antagonists and amiloride analogues at the human alpha2A-adrenergic receptor. Mol Pharmacol. 1998 May;53(5):916-25.

REF 63

A-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 64

Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.

REF 65

Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55.

REF 66

Activation 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 67

Studies of midaglizole (DG-5128). A new type of oral hypoglycemic drug in healthy subjects. Diabetes. 1987 Feb;36(2):216-20.

REF 68

Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.

REF 69

alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. J Med Chem. 1982 Dec;25(12):1389-401.

REF 70

Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.

REF 71

3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferas... J Med Chem. 1999 Jun 3;42(11):1982-90.

REF 72

Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. J Med Chem. 1997 Jan 3;40(1):18-23.

REF 73

Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeu... J Med Chem. 1996 Jan 19;39(2):570-81.

REF 74

Effect of ring size or an additional heteroatom on the potency and selectivity of bicyclic benzylamine-type inhibitors of phenylethanolamine N-meth... J Med Chem. 1996 Aug 30;39(18):3539-46.

REF 75

N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies. J Med Chem. 1998 Oct 8;41(21):4165-70.

REF 76

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