Details of the Drug

General Information of Drug (ID: DMTIGA0)

• Drug Name: Acrivastine
• Synonyms: Acrivastin; Acrivastina; Acrivastinum; Semprex; Acrivastina [Spanish]; Acrivastinum [Latin]; Benadryl allergy relief; BW 0270C; BW 825C; BW A825C; BW-825C; Acrivastine (USAN/INN); Acrivastine [USAN:INN:BAN]; E-(9CI); (2E)-3-{6-[(1E)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-en-1-yl]pyridin-2-yl}prop-2-enoic acid; (E)-3-[6-[(E)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]pyridin-2-yl]prop-2-enoic acid; (E)-6-((E)-3-(1-Pyrrolidinyl)-1-p-tolylpropenyl)-2-pyridineacrylic acid; (E)-6-((E)-3-(1-Pyrrolidinyl-1-p-tolylpropenyl)-2-pyridinacrylsaeure; (E,E)-3-[6-[1-(4-methylphenyl)-3-(1-pyrrolidinyl)-1-propenyl]-2-pyridinyl]-2-propenoic acid; 3-{6-[1-(4-methylphenyl)-3-(pyrrolidin-1-yl)prop-1-en-1-yl]pyridin-2-yl}prop-2-enoic acid

Indication

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[1]
Common cold	CA00	Approved	[2]
Seasonal allergic rhinitis	CA08.01	Approved	[2]
Vasomotor/allergic rhinitis	CA08	Approved	[2]

• Therapeutic Class: Antiinflammatory Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 348.4
  Logarithm of the Partition Coefficient (xlogp); 1.6
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Clearance: The clearance of drug is 2.9 +/- 0.7 mL/min/kg []
  Elimination: 67% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.9 +/- 0.3 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.31116 micromolar/kg/day [5]
  Vd: The volume of distribution (Vd) of drug is 0.46 +/- 0.05 L/kg []
  Water Solubility: The ability of drug to dissolve in water is measured as 0.7 mg/mL [3]
• Chemical Identifiers:
  Formula: C22H24N2O2
  IUPAC Name: (E)-3-[6-[(E)-1-(4-methylphenyl)-3-pyrrolidin-1-ylprop-1-enyl]pyridin-2-yl]prop-2-enoic acid
  Canonical SMILES: CC1=CC=C(C=C1)/C(=C\\CN2CCCC2)/C3=CC=CC(=N3)/C=C/C(=O)O
  InChI: InChI=1S/C22H24N2O2/c1-17-7-9-18(10-8-17)20(13-16-24-14-2-3-15-24)21-6-4-5-19(23-21)11-12-22(25)26/h4-13H,2-3,14-16H2,1H3,(H,25,26)/b12-11+,20-13+
  InChIKey: PWACSDKDOHSSQD-IUTFFREVSA-N
• Cross-matching ID:
  PubChem CID: 5284514
  ChEBI ID: CHEBI:83168
  CAS Number: 87848-99-5
  DrugBank ID: DB09488
  TTD ID: D0O4EU
  VARIDT ID: DR01418
• 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
Histamine H1 receptor (H1R)	TTTIBOJ	HRH1_HUMAN	Antagonist	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Gene/Protein Processing	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Allergic rhinitis
• ICD Disease Classification: CA08.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Histamine H1 receptor (H1R)	DTT	HRH1	6.74E-01	0.13	0.43
P-glycoprotein 1 (ABCB1)	DTP	P-GP	6.54E-01	1.95E-01	4.04E-01

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Phenyltoloxamine	DMKAEQW	Moderate	Additive anticholinergic effects by the combination of Acrivastine and Phenyltoloxamine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[9]
Revefenacin	DMMP5SI	Moderate	Additive anticholinergic effects by the combination of Acrivastine and Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[10]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Acrivastine and Esketamine.	Depression [6A70-6A7Z]	[11]
Belladonna	DM2RBWK	Moderate	Additive anticholinergic effects by the combination of Acrivastine and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[12]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Acrivastine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[13]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Acrivastine and Lasmiditan.	Migraine [8A80]	[14]
Methylscopolamine	DM5VWOB	Moderate	Additive anticholinergic effects by the combination of Acrivastine and Methylscopolamine.	Peptic ulcer [DA61]	[12]

References

• [1] Comparative tolerability of second generation antihistamines. Drug Saf. 1999 May;20(5):385-401.
• [2] Acrivastine FDA Label
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] 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
• [6] Clinical pharmacology of new histamine H1 receptor antagonists. Clin Pharmacokinet. 1999 May;36(5):329-52.
• [7] Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37.
• [8] Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
• [9] Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82. [PMID: 7202232]
• [10] Cole JM, Sheehan AH, Jordan JK "Concomitant use of ipratropium and tiotropium in chronic obstructive plmonary disease." Ann Pharmacother 46 (2012): 1717-21. [PMID: 23170031]
• [11] Cerner Multum, Inc. "Australian Product Information.".
• [12] Cohen MA, Alfonso CA, Mosquera M. Development of urinary retention during treatment with clozapine and meclizine [published correction appears in Am J Psychiatry 1994 Jun;151(6):952]. Am J Psychiatry. 1994;151(4):619-620. [PMID: 8147469]
• [13] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [14] Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.