Details of the Drug

General Information of Drug (ID: DMGFB0E)

• Drug Name: MOXONIDINE
• Synonyms: BDF-5895; BE-5895; Normoxin; AC1OCENE; SCHEMBL1230620; Moxonidine hydrochloride hydrate; moxonidine hydrochloride monohydrate; LY-326869; 4-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methylpyrimidin-5-amine hydrate hydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 241.68
  Logarithm of the Partition Coefficient (xlogp); 0.6
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 15-44 h []
  Bioavailability: 88% 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 11 mL/min/kg [3]
  Elimination: Elimination is nearly entirely via the kidneys with a majority (50 -75%) of overall moxonidine being eliminated unchanged through renal excretion []
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.2 - 2.3 hours []
  Metabolism: The drug is metabolized via opening of the imidazoline ring [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.1182 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.93% [3]
  Vd: The volume of distribution (Vd) of drug is 1.8 +/- 0.4 L/kg []
• Chemical Identifiers:
  Formula: C9H12ClN5O
  IUPAC Name: 4-chloro-N-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-methylpyrimidin-5-amine
  Canonical SMILES: CC1=NC(=C(C(=N1)Cl)NC2=NCCN2)OC
  InChI: InChI=1S/C9H12ClN5O/c1-5-13-7(10)6(8(14-5)16-2)15-9-11-3-4-12-9/h3-4H2,1-2H3,(H2,11,12,15)
  InChIKey: WPNJAUFVNXKLIM-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4810
  ChEBI ID: CHEBI:7009
  CAS Number: 75438-57-2
  DrugBank ID: DB09242
  TTD ID: D0E9PK

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-2A (ADRA2A)	TTWG9A4	ADA2A_HUMAN	Inhibitor	[6]
Adrenergic receptor alpha-2B (ADRA2B)	TTWM4TY	ADA2B_HUMAN	Inhibitor	[6]
Adrenergic receptor alpha-2C (ADRA2C)	TT2NUT5	ADA2C_HUMAN	Inhibitor	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Insulin (INS)	OTZ85PDU	INS_HUMAN	Gene/Protein Processing	[7]

Molecular Expression Atlas of This Drug

• The Studied Disease: Alcohol dependence
• ICD Disease Classification: 6C40.2

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

References

• [1] The role of I(1)-imidazoline and alpha(2)-adrenergic receptors in the modulation of glucose metabolism in the spontaneously hypertensive obese rat ... J Pharmacol Exp Ther. 2003 Aug;306(2):646-57.
• [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] Jiang XL, Samant S, Lesko LJ, Schmidt S: Clinical pharmacokinetics and pharmacodynamics of clopidogrel. Clin Pharmacokinet. 2015 Feb;54(2):147-66. doi: 10.1007/s40262-014-0230-6.
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [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] Selective imidazoline agonist moxonidine in obese hypertensive patients. Int J Clin Pract. 2006 May;60(5):621-9. doi: 10.1111/j.1368-5031.2006.00951.x.