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]
Structure
3D MOL 2D MOL
#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
DrugBank ID
DB01018
VARIDT ID
DR01628
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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.