Details of the Drug

General Information of Drug (ID: DMTV7XH)

• Drug Name: SPN-812
• Synonyms: Viloxazine hydrochloride; 35604-67-2; 2-((2-Ethoxyphenoxy)methyl)morpholine hydrochloride; Emovit; 2-[(2-ethoxyphenoxy)methyl]morpholine hydrochloride; ICI 58,834; Viloxazine hydrochloride [USAN]; 2-((2-ethoxyphenoxy)methyl)morpholinehydrochloride; 2-[(2-ethoxyphenoxy)methyl]morpholine;hydrochloride; Morpholine, 2-[(2-ethoxyphenoxy)methyl]-, hydrochloride; Vicilan; Vivalan; 2-[(2-ethoxy phenoxy)methyl]morpholine hydrochloride; Morpholine, 2-((2-ethoxyphenoxy)methyl)-, hydrochloride; Viloxazine hydrochloride (USAN); Viloxazine HCl; CCRIS 1915; Viloxacina clorhidrato; ICI-58834; Viloxacina clorhidrato [Spanish]; EINECS 252-638-6; Prestwick_734; 2-((o-Ethoxyphenoxy)methyl)morpholine hydrochloride; Vivalan (TN); 2-(2-Ethoxyphenoxymethyl)tetrahydro-1,4-oxazine hydrochloride; 2-(2-Ethoxyphenoxymethyl)-2,3,5,6-tetrahydro-1,4-oxazine hydrochloride; rac Viloxazine Hydrochloride; DSSTox_CID_31511; DSSTox_RID_97396; DSSTox_GSID_57722; SCHEMBL300741; CHEMBL2106483; DTXSID8057722; Tox21_113955; 1478AE; AKOS015847050; CCG-220828; NCGC00262964-01; CAS-35604-67-2; A6217; FT-0675815; FT-0675816; FT-0675817; FT-0675818; FT-0675819; D02572; Z-1958; 2-(o-ethoxyphenoxymethyl)morpholine hydrochloride; 604E672; SR-01000872636; SR-01000872636-1; W-110863; 2-(2-Ethoxy-phenoxymethyl)-morpholine; hydrochloride; 2-[(2-Ethoxyphenoxy)-methyl]morpholine hydrochloride; Q27285797; 2-(2-ethoxy-phenoxymethyl)-tetra-hydro-1,4-oxazine hydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 273.75
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 5
  Hydrogen Bond Donor Count; 2
  Hydrogen Bond Acceptor Count; 4
• ADMET Property:
  Bioavailability: 85% of drug becomes completely available to its intended biological destination(s) [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 2.1 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 4.1 hours [3]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.73 L/kg [3]
• Chemical Identifiers:
  Formula: C13H20ClNO3
  IUPAC Name: 2-[(2-ethoxyphenoxy)methyl]morpholine;hydrochloride
  Canonical SMILES: CCOC1=CC=CC=C1OCC2CNCCO2.Cl
  InChI: InChI=1S/C13H19NO3.ClH/c1-2-15-12-5-3-4-6-13(12)17-10-11-9-14-7-8-16-11;/h3-6,11,14H,2,7-10H2,1H3;1H
  InChIKey: HJOCKFVCMLCPTP-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 71424
  CAS Number: 35604-67-2
  TTD ID: DRL5Y7

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2B receptor (HTR2B)	TT0K1SC	5HT2B_HUMAN	Antagonist	[4]
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Antagonist	[4]

Molecular Expression Atlas of This Drug

• The Studied Disease: Attention deficit hyperactivity disorder
• ICD Disease Classification: 6A05.Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Norepinephrine transporter (NET)	DTT	SLC6A2	7.05E-01	7.02E-03	0.07
5-HT 2B receptor (HTR2B)	DTT	HTR2B	2.08E-01	-0.05	-0.23

References

• [1] ClinicalTrials.gov (NCT04786990) Open-Label Study of SPN-812 Administered With Psychostimulants in Children and Adolescents With ADHD (ADHD). U.S. National Institutes of Health.
• [2] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties. J Exp Pharmacol. 2020 Aug 25;12:285-300.
• [5] Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
• [6] Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
• [7] Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):220-8.
• [8] Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
• [9] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [10] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [11] Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol. 2006 Oct;16(7):481-90.
• [12] Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
• [13] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [14] Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharmacol. 1979 Sep;67(1):79-85.
• [15] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [16] Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model.CPT Pharmacometrics Syst Pharmacol.2014 Apr 23;3:e111.
• [17] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [18] Novel serotonin receptor 2 (5-HT2R) agonists and antagonists: a patent review (2004-2014).Expert Opin Ther Pat. 2016;26(1):89-106.