Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMCX9WN)

• Drug Name: 5-methylurapidil Drug Info
• Synonyms: 5 methylurapidil; 5-methyl-urapidil

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 5640
  CAS Number: CAS 34661-85-3
  TTD Drug ID: DMCX9WN

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor alpha-2C (ADRA2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MOXONIDINE	DMGFB0E	Alcohol dependence	6C40.2	Approved	[6]
Dihydroergocristine	DM5SQ1G	Alcohol dependence	6C40.2	Approved	[7]
Brimonidine	DMQLT4N	Ocular hypertension	9C61.01	Approved	[8]
Amosulalol	DML8QSZ	Hypertension	BA00-BA04	Approved	[9]
Amezinium	DM6I2WQ	Hypotension	BA20-BA21	Approved	[10]
Propylhexedrine	DMTBW2O	Obesity	5B81	Approved	[11]
Tetrahydrozoline	DMT57WC	Ocular disease	1F00.1Z	Approved	[12]
Rilmenidine	DM13PQW	Hypertension	BA00-BA04	Approved	[13]
Xylometazoline	DMKV32D	Allergic rhinitis	CA08.0	Phase 4	[14]
TNX-102	DMO1234	Fibromyalgia	MG30.01	Phase 3	[15]

Drug(s) Targeting Adrenergic receptor alpha-1B (ADRA1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methamphetamine	DMPM4SK	Anxiety		Approved	[16]
Propericiazine	DME9JNL	Psychiatric disorder	6E8Z	Approved	[17]
Methoxamine	DMF5XQH	Hypertension	BA00-BA04	Approved	[18]
Phendimetrazine	DM6TS1N	Obesity	5B81	Approved	[19]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[20]
TIOSPIRONE	DME5QDP	N. A.	N. A.	Discontinued in Phase 3	[21]
Sunepitron	DM6M8ZX	N. A.	N. A.	Discontinued in Phase 3	[22]
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[23]
SOU-001	DMPAEK5	Urinary incontinence	MF50.2	Discontinued in Phase 2	[24]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[25]

Drug(s) Affected By Alpha-1D adrenergic receptor (ADRA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alfuzosin	DMZVMKF	Benign prostatic hyperplasia	GA90	Approved	[26]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[27]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[28]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[5]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]
Terbutaline	DMD4381	Asthma	CA23	Approved	[30]
Methoxamine	DMF5XQH	Hypertension	BA00-BA04	Approved	[5]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[27]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[30]
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[5]

Drug(s) Affected By Alpha-1A adrenergic receptor (ADRA1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamsulosin	DM5QF9V	Benign prostatic hyperplasia	GA90	Approved	[31]
SILODOSIN	DMJSBT6	Benign prostatic hyperplasia	GA90	Approved	[28]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[32]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[27]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[28]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[33]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[31]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[34]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[27]
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-1B (ADRA1B)	TTBRKXS	ADA1B_HUMAN	Antagonist	[2]
Adrenergic receptor alpha-2C (ADRA2C)	TT2NUT5	ADA2C_HUMAN	Antagonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Gene/Protein Processing	[4]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Protein Interaction/Cellular Processes	[5]

References

• [1] 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: 489).
• [2] Affinity of serotonin receptor antagonists and agonists to recombinant and native alpha1-adrenoceptor subtypes. Jpn J Pharmacol. 2001 Jun;86(2):189-95.
• [3] Phe-308 and Phe-312 in transmembrane domain 7 are major sites of alpha 1-adrenergic receptor antagonist binding. Imidazoline agonists bind like ant... J Biol Chem. 2001 Jul 6;276(27):25366-71.
• [4] Functional alpha(1)-adrenoceptor subtypes in human submandibular glands. J Dent Res. 2006 Mar;85(3):251-6. doi: 10.1177/154405910608500309.
• [5] Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to alpha1D subtypes overexpressed in cell membrane. Sci China C Life Sci. 2004 Aug;47(4):376-81. doi: 10.1360/03yc0109.
• [6] 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.
• [7] 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.
• [8] 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).
• [9] 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.
• [10] Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforschung. 1981;31(9a):1558-65.
• [11] Airway compromise and delayed death following attempted central vein injection of propylhexedrine. J Emerg Med. 1994 Nov-Dec;12(6):795-7.
• [12] Prolonged cardiovascular effects after unintentional ingestion of tetrahydrozoline. Clin Toxicol (Phila). 2008 Feb;46(2):171-2.
• [13] Rilmenidine-induced ocular hypotension: role of imidazoline1 and alpha 2 receptors. Curr Eye Res. 1996 Sep;15(9):943-50.
• [14] Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.
• [15] Clinical pipeline report, company report or official report of Tonix Pharmaceuticals.
• [16] Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference. Drug Alcohol Depend. 2009 Jan 1;99(1-3):231-9.
• [17] Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91.
• [18] Activation of alpha1-adrenoceptors inhibits growth hormone secretion in humans. Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):460-2.
• [19] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [20] 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.
• [21] 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem. 1996 Jan 5;39(1):143-8.
• [22] An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment o... J Med Chem. 2006 Jun 1;49(11):3116-35.
• [23] 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.
• [24] Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004 Aug;3(8):673-83.
• [25] Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. J Med Chem. 1995 Sep 15;38(19):3681-716.
• [26] The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8.
• [27] Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. doi: 10.1161/01.cir.97.13.1227.
• [28] Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
• [29] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [30] Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes. J Neuroimmunol. 1999 Mar 1;95(1-2):165-73. doi: 10.1016/s0165-5728(99)00011-9.
• [31] Cell membrane chromatography competitive binding analysis for characterization of 1A adrenoreceptor binding interactions. Anal Bioanal Chem. 2011 Jul;400(10):3625-33. doi: 10.1007/s00216-011-5026-z. Epub 2011 May 5.
• [32] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [33] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [34] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.