Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ8AFT)

• DTT Name: Adrenergic receptor Alpha-2 (ADRA2)
• Synonyms: Alpha-2 adrenergic receptor; Alpha(2)-adrenoceptor
• Gene Name: ADRA2
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: NOUNIPROTAC
• TTD ID: T31424

Molecular Interaction Atlas (MIA) of This DTT

15 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apraclonidine	DMO4PVE	Intra ocular pressure reduction	9C40	Approved	[2]
Brimonidine	DMQLT4N	Ocular hypertension	9C61.01	Approved	[3]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[4]
Dexmedetomidine	DM93L4X	Irritability	MB24	Approved	[5]
Guanabenz	DM5QWEL	High blood pressure	BA00	Approved	[6]
Guanfacine extended release	DMB1CZ8	Attention deficit hyperactivity disorder	6A05.Z	Approved	[7]
Guanidine Hydrochloride	DM0P63W	Muscle fatigue	FB32.5	Approved	[8]
Lofexidine	DM1WXA6	Heroin and opiate withdrawal	6C43	Approved	[1]
Meperidine	DMX4GND	Pain	MG30-MG3Z	Approved	[9]
Methyldopate Hydrochloride	DM8XI09	Hypertension	BA00-BA04	Approved	[10]
Nicergoline	DMBCM8L	Brain ischaemia	8B1Z	Approved	[11]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[12]
Sodium chloride	DMM3950	Skin burns	ME65.0	Approved	[4]
Tizanidine	DMR2IQ4	Spasm	MB47.3	Approved	[13]
Yohimbine	DMJCP1Y	Erectile dysfunction	HA01.1	Approved	[14]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fadolmidine	DM6RKG3	Neuropathic pain	8E43.0	Phase 2	[15]
Fipamezole	DMG439E	Acute myeloid leukaemia	2A60	Phase 2	[16]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mivazerol	DMXT36M	Angina pectoris	BA40	Discontinued in Phase 3	[17]
Atipamezole	DM10XWU	Male sexual disorder	HA02.0	Discontinued in Phase 2	[18]
ADX415	DM61AV4	Hypertension	BA00-BA04	Terminated	[19]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Brominide tartrate	DMMC4BY	Discovery agent	N.A.	Investigative	[20]
[3H]rauwolscine	DMBQZ2H	Discovery agent	N.A.	Investigative	[21]

References

• [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.
• [2] 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.
• [3] Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma. Arthritis Rheum. 2000 Aug;43(8):1886-90.
• [4] 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.
• [5] Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anesthesiol. 2002 Oct;16(6):587-95.
• [6] Centrally acting sympathetic inhibitors for therapy of patients with hypertension. Nippon Rinsho. 1997 Aug;55(8):2081-5.
• [7] Emerging drugs for attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34.
• [8] Guanidine-based 2-adrenoceptor ligands: Towards selective antagonist activity.Eur J Med Chem.2014 Jul 23;82:242-54.
• [9] 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.
• [10] Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders
• [11] Effect of non-selective alpha-adrenergic receptor antagonist nicergoline on the activity of neurons in the ventral lateral thalamic nucleus. Fiziol Zh. 2005;51(4):29-35.
• [12] Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55.
• [13] 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.
• [14] Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol (Phila). 2009 Sep;47(8):827-9.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Emerging drugs for Parkinson's disease. Expert Opin Emerg Drugs. 2006 Sep;11(3):403-17.
• [17] Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999 Feb;54(2):146-65.
• [18] 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.
• [19] Clinical pipeline report, company report or official report of Shionogi (2011).
• [20] 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.
• [21] Characterization of alpha-adrenoceptor subtypes in smooth muscle of equine ileum. Am J Vet Res. 2001 Sep;62(9):1370-4.