Details of the Drug

General Information of Drug (ID: DM8WBAH)

• Drug Name: Dexmethylphenidate hydrochloride
• Synonyms: Dexmethylphenidate hydrochloride; Focalin; D-threo-Methylphenidate hydrochloride; Dexmethylphenidate HCl; Focalin XR; UNII-1678OK0E08; Dexmethylphenidate hydrochloride [USAN]; 19262-68-1; 1678OK0E08; 23655-65-4; CHEMBL904; Methyl (2R)-phenyl((2R)-piperidin-2-yl)acetate hydrochloride; dl-threo-Methylphenidate Hydrochloride; 2-Piperidineacetic acid, alpha-phenyl-, methyl ester, hydrochloride, (R-(R*,R*))-; 2-Piperidineacetic acid, alpha-phenyl-, methyl ester, hydrochloride, (alphaR,2R)-; Dexmethylphenidate; NWP06

Indication

Disease Entry	ICD 11	Status	REF
Attention deficit hyperactivity disorder	6A05.Z	Approved	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight; 269.77
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 4
  Hydrogen Bond Donor Count; 2
  Hydrogen Bond Acceptor Count; 3
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3-6 h [3]
  Bioavailability: The bioavailability of drug is 32% [3]
  Clearance: The renal clearance of drug is 0.005 L/h/kg [4]
  Elimination: Dexmethylphenidate is mainly eliminated renally, and 90% of the dose is collected in the urine and 3.3% is collected from feces [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.2 hours [6]
  Metabolism: The drug is metabolized via the carboxylesterase 1A1 in the liver [5]
  Vd: The volume of distribution (Vd) of drug is 2.65 L/kg [5]
• Chemical Identifiers:
  Formula: C14H20ClNO2
  IUPAC Name: methyl (2R)-2-phenyl-2-[(2R)-piperidin-2-yl]acetate;hydrochloride
  Canonical SMILES: COC(=O)[C@@H]([C@H]1CCCCN1)C2=CC=CC=C2.Cl
  InChI: InChI=1S/C14H19NO2.ClH/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12;/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3;1H/t12-,13-;/m1./s1
  InChIKey: JUMYIBMBTDDLNG-OJERSXHUSA-N
• Cross-matching ID:
  PubChem CID: 154100
  CAS Number: 19262-68-1
  TTD ID: D02QCD
  VARIDT ID: DR00844

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine transporter (DAT)	TTVBI8W	SC6A3_HUMAN	Inhibitor	[7]

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
Dopamine transporter (DAT)	DTT	SLC6A3	1.08E-03	-3.08	-1.99

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033419)
• [3] Zepatier FDA label
• [4] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [5] Latini R, Tognoni G, Kates RE: Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet. 1984 Mar-Apr;9(2):136-56. doi: 10.2165/00003088-198409020-00002.
• [6] Dose-proportional and stereospecific pharmacokinetics of methylphenidate delivered using an osmotic, controlled-release oral delivery system. J Clin Pharmacol. 2000 Oct;40(10):1141-9.
• [7] Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate. J Med Chem. 2007 May 31;50(11):2718-31.
• [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] Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults. Neuropsychopharmacology. 2015 Nov;40(12):2745-52.
• [10] Imaging the effects of methylphenidate on brain dopamine: new model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1410-5.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7.
• [13] Rapid detection of Parkinson's disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse. 1998 Jun;29(2):128-41.
• [14] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [15] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 927).