Details of the Drug

General Information of Drug (ID: DMCYANK)

• Drug Name: Doxapram
• Synonyms: Docatone; Dopram; Doxapramum; Doxapram HCL; Doxapram hydrochloride; Docatone (TN); Dopram (TN); Doxapram (INN); Doxapram [USP:JAN]; Doxapramum [INN-Latin]; (+-)-doxapram; 1-Ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone; 1-ethyl-4-(2-morpholin-4-ylethyl)-3,3-diphenylpyrrolidin-2-one; 1-ethyl-4-[2-(morpholin-4-yl)ethyl]-3,3-diphenylpyrrolidin-2-one; 2-Pyrrolidinone, 1-ethyl-4-(2-(4-morpholinyl)ethyl)-3,3-diphenyl-(9CI)

Indication

Disease Entry	ICD 11	Status	REF
Respiratory disease	CB40	Approved	[1]

• Therapeutic Class: Central Nervous System Stimulants
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 378.5
  Logarithm of the Partition Coefficient (xlogp); 3.3
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Bioavailability: 64% 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 5.3 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 4.1 hours [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 10.5675 micromolar/kg/day [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.2 L/kg [3]
• Chemical Identifiers:
  Formula: C24H30N2O2
  IUPAC Name: 1-ethyl-4-(2-morpholin-4-ylethyl)-3,3-diphenylpyrrolidin-2-one
  Canonical SMILES: CCN1CC(C(C1=O)(C2=CC=CC=C2)C3=CC=CC=C3)CCN4CCOCC4
  InChI: InChI=1S/C24H30N2O2/c1-2-26-19-22(13-14-25-15-17-28-18-16-25)24(23(26)27,20-9-5-3-6-10-20)21-11-7-4-8-12-21/h3-12,22H,2,13-19H2,1H3
  InChIKey: XFDJYSQDBULQSI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3156
  ChEBI ID: CHEBI:681848
  CAS Number: 309-29-5
  DrugBank ID: DB00561
  TTD ID: D0M7BT
  INTEDE ID: DR0541

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peripheral carotid chemoreceptor (PCC)	TT6EYVN	NOUNIPROTAC	Stimulator	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Gene/Protein Processing	[7]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Doxapram (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Major	Additive hypertensive effects by the combination of Doxapram and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[8]
Linezolid	DMGFPU2	Major	Increased risk of hyperpyrexia by the combination of Doxapram and Linezolid.	Bacterial infection [1A00-1C4Z]	[8]
Selegiline	DM6034S	Major	Increased risk of hyperpyrexia by the combination of Doxapram and Selegiline.	Depression [6A70-6A7Z]	[8]
Isocarboxazid	DMAF1NB	Major	Increased risk of hyperpyrexia by the combination of Doxapram and Isocarboxazid.	Depression [6A70-6A7Z]	[8]
Tranylcypromine	DMGB5RE	Major	Increased risk of hyperpyrexia by the combination of Doxapram and Tranylcypromine.	Depression [6A70-6A7Z]	[8]
Phenelzine	DMHIDUE	Major	Increased risk of hyperpyrexia by the combination of Doxapram and Phenelzine.	Depression [6A70-6A7Z]	[8]
Esketamine	DMVU687	Major	Additive hypertensive effects by the combination of Doxapram and Esketamine.	Depression [6A70-6A7Z]	[9]
Procarbazine	DMIK367	Major	Additive hypertensive effects by the combination of Doxapram and Procarbazine.	Hodgkin lymphoma [2B30]	[8]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of lowers seizure threshold by the combination of Doxapram and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[10]
Ozanimod	DMT6AM2	Major	Increased risk of hyperpyrexia by the combination of Doxapram and Ozanimod.	Multiple sclerosis [8A40]	[8]
Bupropion	DM5PCS7	Major	Increased risk of lowers seizure threshold by the combination of Doxapram and Bupropion.	Nicotine use disorder [6C4A]	[11]
Safinamide	DM0YWJC	Moderate	Decreased metabolism of Doxapram caused by Safinamide mediated inhibition of non-CYP450 enzyme.	Parkinsonism [8A00]	[12]
Rasagiline	DM3WKQ4	Moderate	Additive hypertensive effects by the combination of Doxapram and Rasagiline.	Parkinsonism [8A00]	[8]

References

• [1] 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. (Ligand id: 7169).
• [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] 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
• [5] Ovalbumin sensitization alters the ventilatory responses to chemical challenges in guinea pigs. J Appl Physiol (1985). 2005 Nov;99(5):1782-8.
• [6] Population pharmacokinetics of doxapram in low-birth-weight Japanese infants with apnea. Eur J Pediatr. 2015 Apr;174(4):509-18.
• [7] Doxapram-induced panic attacks and cortisol elevation. Psychiatry Res. 2005 Feb 28;133(2-3):253-61. doi: 10.1016/j.psychres.2004.10.010.
• [8] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
• [9] Cerner Multum, Inc. "Australian Product Information.".
• [10] Product Information. Suprep Bowel Prep Kit (magnesium/potassium/sodium sulfates). Braintree Laboratories, Braintree, MA.
• [11] Product Information. Wellbutrin XL (buPROPion). GlaxoSmithKline, Philadelphia, PA.
• [12] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".