Details of the Drug

General Information of Drug (ID: DMT57WC)

• Drug Name: Tetrahydrozoline
• Synonyms: Tyzine

Indication

Disease Entry	ICD 11	Status	REF
Ocular disease	1F00.1Z	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 200.28
  Topological Polar Surface Area (xlogp); 1.8
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 0.068-0.380 mcg/L [2]
  Elimination: Following ocular administration of 0.05% tetryzoline, tetryzoline was detected in urine at 24 hours [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 6 hours [3]
• Chemical Identifiers:
  Formula: C13H16N2
  IUPAC Name: 2-(1,2,3,4-tetrahydronaphthalen-1-yl)-4,5-dihydro-1H-imidazole
  Canonical SMILES: C1CC(C2=CC=CC=C2C1)C3=NCCN3
  InChI: InChI=1S/C13H16N2/c1-2-6-11-10(4-1)5-3-7-12(11)13-14-8-9-15-13/h1-2,4,6,12H,3,5,7-9H2,(H,14,15)
  InChIKey: BYJAVTDNIXVSPW-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5419
  ChEBI ID: CHEBI:28674
  CAS Number: 84-22-0
  DrugBank ID: DB06764
  TTD ID: D05IHU

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-2C (ADRA2C)	TT2NUT5	ADA2C_HUMAN	Modulator	[1], [4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Ocular disease
• ICD Disease Classification: 1F00.1Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Adrenergic receptor alpha-2C (ADRA2C)	DTT	ADRA2C	1.76E-01	-0.06	-0.28

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Tetrahydrozoline (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Moderate	Decreased metabolism of Tetrahydrozoline caused by Methylene blue mediated inhibition of non-CYP450 enzyme.	Acquired methaemoglobinaemia [3A93]	[15]
Levomilnacipran	DMV26S8	Moderate	Increased risk of rapid heart rate by the combination of Tetrahydrozoline and Levomilnacipran.	Chronic pain [MG30]	[16]
Ozanimod	DMT6AM2	Moderate	Increased risk of hyperpyrexia by the combination of Tetrahydrozoline and Ozanimod.	Multiple sclerosis [8A40]	[17]

References

• [1] Prolonged cardiovascular effects after unintentional ingestion of tetrahydrozoline. Clin Toxicol (Phila). 2008 Feb;46(2):171-2.
• [2] Stillwell ME, Saady JJ: Use of tetrahydrozoline for chemical submission. Forensic Sci Int. 2012 Sep 10;221(1-3):e12-6. doi: 10.1016/j.forsciint.2012.04.004. Epub 2012 May 1.
• [3] Tetrahydrozoline (Visine(R)) concentrations in serum and urine during therapeutic ocular dosing: a necessary first step in determining an overdose. Clin Toxicol (Phila). 2011 Nov;49(9):810-4. doi: 10.3109/15563650.2011.615064. Epub 2011 Oct 5.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] 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.
• [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.
• [7] 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).
• [8] 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.
• [9] Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforschung. 1981;31(9a):1558-65.
• [10] Airway compromise and delayed death following attempted central vein injection of propylhexedrine. J Emerg Med. 1994 Nov-Dec;12(6):795-7.
• [11] Rilmenidine-induced ocular hypotension: role of imidazoline1 and alpha 2 receptors. Curr Eye Res. 1996 Sep;15(9):943-50.
• [12] Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.
• [13] Clinical pipeline report, company report or official report of Tonix Pharmaceuticals.
• [14] 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.
• [15] Cusson JR, Goldenberg E, Larochelle P "Effect of a novel monoamine-oxidase inhibitor, moclobemide on the sensitivity to intravenous tyramine and norepinephrine in humans." J Clin Pharmacol 31 (1991): 462-7. [PMID: 2050833]
• [16] Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
• [17] Hunter KR, Boakes AJ, Laurence DR, Stern GM "Monoamine oxidase inhibitors and L-dopa." Br Med J 3 (1970): 388. [PMID: 5451592]