Details of the Drug

General Information of Drug (ID: DMPN5IH)

• Drug Name: Guanfacine
• Synonyms: GUANFACINE; Tenex; Guanfacinum [INN-Latin]; Guanfacina [INN-Spanish]; Estulic; Intuniv; N-amidino-2-(2,6-dichlorophenyl)acetamide; CHEBI:5558; INJOMKTZOLKMBF-UHFFFAOYSA-N; SPD 503; C9H9Cl2N3O; N-carbamimidoyl-2-(2,6-dichlorophenyl)acetamide; N-(diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide; Guanfacine Monohydrochloride; NCGC00015469-05; Lon798; Guanfacine (INN); Estulic (TN); Tenex (Salt/Mix); Estulic (Salt/Mix); Tocris-1030; Prestwick1_000339; Prestwick3_000339; Prestwick2_000339; Prestwick0_000339; Lopac-G-1043

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[1]
Alzheimer disease	8A20	Phase 3	[2]

• Affected Organisms: Humans and other mammals
• ATC Code:
  C02AC02: Guanfacine
  C02AC: Imidazoline receptor agonists
  C02A: ANTIADRENERGIC AGENTS, CENTRALLY ACTING
  C02: ANTIHYPERTENSIVES
  C: CARDIOVASCULAR SYSTEM
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 246.09
  Logarithm of the Partition Coefficient; Not Available
  Rotatable Bond Count; 2
  Hydrogen Bond Donor Count; 2
  Hydrogen Bond Acceptor Count; 1
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 56 +/- 15 mcgh/L [3]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 2.5 +/- 0.6 mcg/L [3]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3 h [3]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
  Bioavailability: The bioavailability of drug is 80% [3]
  Clearance: The renal clearance of drug is 233 +/- 245 mL/min [5]
  Elimination: Guanfacine is 57.0 +/- 32.0% eliminated in the urine in patients with normal renal function [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 17 hours [3]
  Metabolism: The drug is metabolized via the CYP3A4 to it's main metabolite 3-hydroxyguanfacine [6]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3483 micromolar/kg/day [7]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.28% [8]
  Vd: The volume of distribution (Vd) of drug is 6.3 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [4]
• Chemical Identifiers:
  Formula: C9H9Cl2N3O
  IUPAC Name: N-(diaminomethylidene)-2-(2,6-dichlorophenyl)acetamide
  Canonical SMILES: C1=CC(=C(C(=C1)Cl)CC(=O)N=C(N)N)Cl
  InChI: InChI=1S/C9H9Cl2N3O/c10-6-2-1-3-7(11)5(6)4-8(15)14-9(12)13/h1-3H,4H2,(H4,12,13,14,15)
  InChIKey: INJOMKTZOLKMBF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3519
  ChEBI ID: CHEMBL862
  CAS Number: 29110-47-2
  UNII: 30OMY4G3MK
  DrugBank ID: DB01018
  VARIDT ID: DR01628
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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	Agonist	[9]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

References

• [1] Guanfacine FDA Label
• [2] ClinicalTrials.gov (NCT03116126) Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease. U.S.National Institutes of Health.
• [3] Guanfacine Extended-Release Tablets (Intuniv), a Nonstimulant Selective Alpha(2A)-Adrenergic Receptor Agonist For Attention-Deficit/Hyperactivity Disorder. P T. 2010 Aug;35(8):448-51.
• [4] BDDCS applied to over 900 drugs
• [5] Kirch W, Kohler H, Braun W: Elimination of guanfacine in patients with normal and impaired renal function. Br J Clin Pharmacol. 1980;10 Suppl 1:33S-35S. doi: 10.1111/j.1365-2125.1980.tb04902.x.
• [6] Iwasaki K: Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metab Pharmacokinet. 2007 Oct;22(5):328-35.
• [7] 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
• [8] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [9] Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
• [10] An in vitro evaluation of guanfacine as a substrate for P-glycoprotein. Neuropsychiatr Dis Treat. 2011;7:501-5.