Target Information

Target General Information

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Target ID

T31424 (Former ID: TTDS00031)

Target Name

Adrenergic receptor Alpha-2 (ADRA2)

Synonyms

Alpha-2 adrenergic receptor; Alpha(2)-adrenoceptor

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 16 Target-related Diseases

Attention deficit hyperactivity disorder [ICD-11: 6A05]

Breathing abnormality [ICD-11: MD11]

Cerebral ischaemia [ICD-11: 8B1Z]

Dementia [ICD-11: 6D80-6D8Z]

Essential hypertension [ICD-11: BA00]

Eyelid inflammatory disorder [ICD-11: 9A02]

Glaucoma [ICD-11: 9C61]

Hypertension [ICD-11: BA00-BA04]

Mood/affect symptom [ICD-11: MB24]

Muscle disorder [ICD-11: FB32-FB3Z]

Opioid use disorder [ICD-11: 6C43]

Optic nerve disorder [ICD-11: 9C40]

Pain [ICD-11: MG30-MG3Z]

Sexual dysfunction [ICD-11: HA00-HA01]

Skin sensation disturbance [ICD-11: ME65]

Tonus and reflex abnormality [ICD-11: MB47]

BioChemical Class

GPCR rhodopsin

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 12 Approved Drugs

Apraclonidine

Drug Info

Approved

Intra ocular pressure reduction

[3], [6]

Brimonidine

Drug Info

Approved

Ocular hypertension

[7], [8]

Clonidine

Drug Info

Approved

Hypertension

[9], [10]

Guanabenz

Drug Info

Approved

High blood pressure

[11], [12]

Guanfacine extended release

Drug Info

Approved

Attention deficit hyperactivity disorder

[13]

Guanidine Hydrochloride

Drug Info

Approved

Muscle fatigue

[5]

Lofexidine

Drug Info

Approved

Opioid dependence

[14]

Meperidine

Drug Info

Approved

Pain

[5]

Oxymetazoline

Drug Info

Approved

Eye inflammation

[5]

Sodium chloride

Drug Info

Approved

Skin burns

[5]

Tizanidine

Drug Info

Approved

Spasm

[3], [15]

Yohimbine

Drug Info

Approved

Erectile dysfunction

[16], [17]

Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

Fadolmidine

Drug Info

Phase 2

Neuropathic pain

[18]

Fipamezole

Drug Info

Phase 2

Acute myeloid leukaemia

[19]

Discontinued Drug(s)

[+] 2 Discontinued Drugs

Atipamezole

Drug Info

Discontinued in Phase 2

Male sexual disorder

[21]

ADX415

Drug Info

Terminated

Hypertension

[22]

Mode of Action

[+] 3 Modes of Action

Agonist

[+] 12 Agonist drugs

Apraclonidine

Drug Info

[23], [24]

Brimonidine

Drug Info

[25]

Clonidine

Drug Info

[26], [27], [28]

Guanabenz

Drug Info

[29]

Guanfacine extended release

Drug Info

[13]

Lofexidine

Drug Info

[1], [31]

Meperidine

Drug Info

[32], [33]

Oxymetazoline

Drug Info

[34]

Sodium chloride

Drug Info

[26]

Tizanidine

Drug Info

[35]

Fadolmidine

Drug Info

[18]

Brominide tartrate

Drug Info

[34], [40], [41]

Modulator

[+] 1 Modulator drugs

Guanidine Hydrochloride

Drug Info

[30]

Antagonist

[+] 4 Antagonist drugs

Yohimbine

Drug Info

[17], [36], [37]

Fipamezole

Drug Info

[38]

Atipamezole

Drug Info

[39]

ADX415

Drug Info

[22]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(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

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

Top

REF 1

Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis. Am J DrugAlcohol Abuse. 2008;34(5):611-6.

REF 2

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: 521).

REF 3

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 4

Drug information of Nicergoline, 2008. eduDrugs.

REF 5

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

REF 6

REF 7

REF 8

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

REF 9

REF 10

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 070315.

REF 11

REF 12

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 074149.

REF 13

Emerging drugs for attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34.

REF 14

2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.

REF 15

REF 16

REF 17

Interest of alpha2-adrenergic agonists and antagonists in clinical practice: background, facts and perspectives. Curr Top Med Chem. 2007;7(2):187-94.

REF 18

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

REF 19

ClinicalTrials.gov (NCT00559871) Safety and Efficacy Study of Fipamezole in Treatment of Motor Dysfunctions in Parkinson's Disease. U.S. National Institutes of Health.

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 800002725)

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 800000275)

REF 22

Clinical pipeline report, company report or official report of Shionogi (2011).

REF 23

Apraclonidine attenuates the increases in spinal excitatory amino acid release in rats with adjuvant-induced inflammation. Anesth Analg. 2002 Mar;94(3):701-5; table of contents.

REF 24

Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)-adrenoceptors and not by an action on imidazoline receptors. Brain Res. 2001 Jun 15;904(1):126-36.

REF 25

Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma. Arthritis Rheum. 2000 Aug;43(8):1886-90.

REF 26

Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats. Pharmacol Biochem Behav. 2000 Nov;67(3):397-403.

REF 27

The alpha2 -adrenergic receptors in hypertension and heart failure: experimental and clinical studies. J Hypertens. 2001 Dec;19(12):2115-24.

REF 28

Effects of intrathecal vs. systemic clonidine in treating chronic allodynia-like response in spinally injured rats. Brain Res. 1996 Oct 14;736(1-2):28-34.

REF 29

Centrally acting sympathetic inhibitors for therapy of patients with hypertension. Nippon Rinsho. 1997 Aug;55(8):2081-5.

REF 30

Guanidine-based 2-adrenoceptor ligands: Towards selective antagonist activity.Eur J Med Chem.2014 Jul 23;82:242-54.

REF 31

A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Drug Alcohol Depend. 2008 Sep 1;97(1-2):158-68.

REF 32

Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor ... Eur J Pharmacol. 2008 Mar 17;582(1-3):70-7.

REF 33

Meperidine exerts agonist activity at the alpha(2B)-adrenoceptor subtype. Anesthesiology. 2002 Jun;96(6):1420-6.

REF 34

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

REF 35

Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52.

REF 36

Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol (Phila). 2009 Sep;47(8):827-9.

REF 37

Alpha2-adrenergic receptors attenuate secretagogue-induced endocytosis and promote exocytosis of intestinal NHE2 and NHE3. J Pharmacol Exp Ther. 2009 Sep;330(3):818-25.

REF 38

Emerging drugs for Parkinson's disease. Expert Opin Emerg Drugs. 2006 Sep;11(3):403-17.

REF 39

Low doses of alpha 2-adrenoceptor antagonists augment spinal morphine analgesia and inhibit development of acute and chronic tolerance. Br J Pharmacol. 2008 Dec;155(8):1264-78.

REF 40

Alpha(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.

REF 41

Brimonidine. A review of its pharmacological properties and clinical potential in the management of open-angle glaucoma and ocular hypertension. Drugs Aging. 1998 Mar;12(3):225-41.

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