Details of the Drug

General Information of Drug (ID: DMO5SZX)

Drug Name

Diphenoxylate

Synonyms

Difenossilato; Difenoxilato; Diphenoxalate; Diphenoxylatum; Difenossilato [DCIT]; Difenoxilato [Spanish]; Diphenoxylate HCl; Diphenoxylate Monohydrochloride; Diphenoxylate hydrochloride; Diphenoxylatum [Latin]; NIH 7562; R 1132; Difenoxilato [INN-Spanish]; Diphenoxylate (INN); Diphenoxylate [INN:BAN]; Diphenoxylate hydrochloride (USP); Diphenoxylate hydrochloride(usp); Diphenoxylatum [INN-Latin]; R 1132 (antiperistaltic); R-1132; Co-phenotrope (TN); Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotate; Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotate monohydrochloride; Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylate; Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylate; Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylate hydrochloride; Isonipecotic acid, 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-, ethyl ester; Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidin-1-ium-4-carboxylate chloride; Isonipecotic acid, 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-, ethyl ester, hydrochloride; 1-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylic acid ethyl ester; 1-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-isonipecotic acid ethyl ester; 1-(3-Cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid ethyl ester hydrochloride; 1-(3-cyano-3,3-diphenylpropyl)-4-(ethoxycarbonyl)-4-phenylpiperidinium chloride; 2,2-Diphenyl-4-(4-carbethoxy-4-phenylpiperidino)butyronitrile; 4-Ethoxycarbonyl-alpha,alpha,4-triphenyl-1-piperidinebutyronitrile, hydrochloride; 4-Piperidinecarboxylic acid, 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-, ethyl ester; 4-Piperidinecarboxylic acid, 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-, ethyl ester (9CI); 4-Piperidinecarboxylic acid, 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-, ethyl ester, monohydrochloride; 4-ethoxycarbonyl-alpha,alpha,4-triphenyl-1-piperidinebutyronitrile hydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Diarrhea	ME05.1	Approved	[1]
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Therapeutic Class

Analgesics

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

452.6

Logarithm of the Partition Coefficient (xlogp)

5.7

Rotatable Bond Count (rotbonds)

9

Hydrogen Bond Donor Count (hbonddonor)

0

Hydrogen Bond Acceptor Count (hbondacc)

4

ADMET Property

Absorption: The absorption of drug is 90% []
Half-life: The concentration or amount of drug in body reduced by one-half in 12 - 14 hours [2]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.63127 micromolar/kg/day [3]

Chemical Identifiers

Formula: C30H32N2O2
IUPAC Name: ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylate
Canonical SMILES: CCOC(=O)C1(CCN(CC1)CCC(C#N)(C2=CC=CC=C2)C3=CC=CC=C3)C4=CC=CC=C4
InChI: InChI=1S/C30H32N2O2/c1-2-34-28(33)29(25-12-6-3-7-13-25)18-21-32(22-19-29)23-20-30(24-31,26-14-8-4-9-15-26)27-16-10-5-11-17-27/h3-17H,2,18-23H2,1H3
InChIKey: HYPPXZBJBPSRLK-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 13505
ChEBI ID: CHEBI:4639
CAS Number: 915-30-0
DrugBank ID: DB01081
TTD ID: D0J2TN

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Agonist	[4]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Diarrhea

ICD Disease Classification

ME05.1

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Opioid receptor mu (MOP)	DTT	OPRM1	5.94E-01	-0.02	-0.17

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Diphenoxylate and Esketamine.	Depression [6A70-6A7Z]	[6]
Levomethadyl Acetate	DM06HG5	Moderate	Additive antimotility effects by the combination of Diphenoxylate and Levomethadyl Acetate.	Opioid use disorder [6C43]	[7]
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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: 7164).
2	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3	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
4	Loperamide: a pharmacological review. Rev Gastroenterol Disord. 2007;7 Suppl 3:S11-8.
5	Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
6	Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
7	Cerner Multum, Inc. "UK Summary of Product Characteristics.".