Details of the Drug

General Information of Drug (ID: DMI7DZ2)

• Drug Name: Prilocaine
• Synonyms: Citanest; Prilocaina; Prilocainum; Propitocaine; Prilocaine [USAN]; Prilocaine base; Astra 1512; Astra 1515; L 67; Citanest (TN); Prilocaina [INN-Spanish]; Prilocainum [INN-Latin]; Propitocaine (JAN); Prilocaine (USP/INN); O-Methyl-2-propylaminopropionanilide; O-Methyl-alpha-propylaminopropionanilide; Alpha-n-Propylamino-2-methylpropionanilide; N-[2-Methylphenyl]-2-[propylamino]propanamide; N-(2-methylphenyl)-N2-propylalaninamide; N-(2-Methylphenyl)-2-(propylamino)propanamide; N-(2-methylphenyl)-N(2)-propylalaninamide; Propanamide, N-(2-methylphenyl)-2-(propylamino)-(9CI); 2-(Propylamino)-o-propionotoluidide; 2-Methyl-.alpha.-propylaminopropionanilide; 2-Methyl-alpha-propylaminopropionanilide

Indication

Disease Entry	ICD 11	Status	REF
Pain	MG30-MG3Z	Approved	[1]
Premature ejaculation	HA03.0Z	Investigative	[2]

• Therapeutic Class: Anesthetics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 220.31
  Logarithm of the Partition Coefficient (xlogp); 2.1
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 29 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.8 hours [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 33.5136 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.72% [3]
  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 3.7 L/kg [3]
• Chemical Identifiers:
  Formula: C13H20N2O
  IUPAC Name: N-(2-methylphenyl)-2-(propylamino)propanamide
  Canonical SMILES: CCCNC(C)C(=O)NC1=CC=CC=C1C
  InChI: InChI=1S/C13H20N2O/c1-4-9-14-11(3)13(16)15-12-8-6-5-7-10(12)2/h5-8,11,14H,4,9H2,1-3H3,(H,15,16)
  InChIKey: MVFGUOIZUNYYSO-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4906
  ChEBI ID: CHEBI:8404
  CAS Number: 721-50-6
  DrugBank ID: DB00750
  TTD ID: D06LYG
• 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
Voltage-gated sodium channel alpha Nav1.5 (SCN5A)	TTZOVE0	SCN5A_HUMAN	Blocker	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Gene/Protein Processing	[6]
Nitric oxide synthase, inducible (NOS2)	OTKKIOJ1	NOS2_HUMAN	Gene/Protein Processing	[6]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Post-Translational Modifications	[6]

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Isosorbide dinitrate	DMBI4JG	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Isosorbide dinitrate.	Anal fissure/fistula [DB50]	[7]
Amyl nitrite	DMJKO05	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Amyl nitrite.	Angina pectoris [BA40]	[7]
Sulfamethoxazole	DMB08GE	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Sulfamethoxazole.	Bacterial infection [1A00-1C4Z]	[7]
Silver sulfadiazine	DMVTHWQ	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Silver sulfadiazine.	Bacterial infection [1A00-1C4Z]	[8]
Levobupivacaine	DM783CH	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Levobupivacaine.	Corneal disease [9A76-9A78]	[7]
Benzocaine	DMI18HW	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Benzocaine.	Corneal disease [9A76-9A78]	[8]
Phenobarbital	DMXZOCG	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Phenobarbital.	Epilepsy/seizure [8A61-8A6Z]	[7]
Isosorbide mononitrate	DMYLMU0	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Isosorbide mononitrate.	Hydrocephalus [8D64]	[7]
Tafenoquine	DM1XT4N	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Tafenoquine.	Malaria [1F40-1F45]	[7]
Primaquine	DMWQ16I	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Primaquine.	Malaria [1F40-1F45]	[7]
Sulphadoxine	DMZI2UF	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Sulphadoxine.	Malaria [1F40-1F45]	[7]
Metoclopramide	DMFA5MY	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Metoclopramide.	Nausea/vomiting [MD90]	[7]
Sulfasalazine	DMICA9H	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Sulfasalazine.	Rheumatoid arthritis [FA20]	[7]
Tetracaine	DM9J6C2	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Tetracaine.	Sensation disturbance [MB40]	[8]
Mepivacaine	DMH2NMY	Major	Increased risk of methemoglobinemia by the combination of Prilocaine and Mepivacaine.	Sensation disturbance [MB40]	[7]
Bretylium	DM1FX74	Moderate	Increased risk of bradycardia by the combination of Prilocaine and Bretylium.	Ventricular tachyarrhythmia [BC71]	[9]
Amiodarone	DMUTEX3	Moderate	Increased risk of bradycardia by the combination of Prilocaine and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[9]

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: 7276).
• [2] Prilocaine FDA Label
• [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] Monoamine transporter and sodium channel mechanisms in the rapid pressor response to cocaine. Pharmacol Biochem Behav. 1998 Feb;59(2):305-12.
• [6] Inflammatory signal transduction pathways induced by prilocaine toxicity in cultured ARPE-19 cells. J Biochem Mol Toxicol. 2023 Dec;37(12):e23491. doi: 10.1002/jbt.23491. Epub 2023 Aug 10.
• [7] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [8] Cerner Multum, Inc. "Australian Product Information.".
• [9] Keidar S, Grenadier E, Palant A "Sinoatrial arrest due to lidocaine injection in sick sinus syndrome during amiodarone administration." Am Heart J 104 (1982): 1384-5. [PMID: 7148661]