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: CHEBI:5558
  CAS Number: 29110-47-2
  UNII: 30OMY4G3MK
  DrugBank ID: DB01018
  VARIDT ID: DR01628
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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.