Details of the Drug

General Information of Drug (ID: DMZBU15)

• Drug Name: Tripelennamine
• Synonyms: Benzoxale; Cizaron; Dehistin; Piribenzil; Pyribenzamin; Pyribenzamine; Pyridbenzamine; Resistamine; Tonaril; Tripelannamine; Tripelenamina; Tripelenamine; Tripelennamin; Tripelennamina; Tripelennaminum; Tripellenamine; Triplennamine; Vetibenzamina; Pyrinamine base; Tripelennamina [Italian]; Tripelennamine [BAN]; Tripelennamine [INN]; Ts and Blues; Pyribenzamine (TN); Pyristine (piristina); Tripelenamina [INN-Spanish]; Tripelennamine (INN); Tripelennaminum [INN-Latin]; Tripelennamine Citrate (1:1); Beta-Dimethylaminoethyl-2-pyridylaminotoluene; Beta-Dimethylaminoethyl-2-pyridylbenzylamine; Benzyl-(alpha-pyridyl)-dimethylaethylendiamin; Benzyl-(alpha-pyridyl)-dimethylaethylendiamin [German]; Benzyl-(alpha.-pyridyl)-dimethylaethylendiamin; Benzyl-.alpha.-pyridyl-dimethyl-aethylendiamin; N-benzyl-N-[2-(dimethylamino)ethyl]pyridin-2-amine; N-Benzyl-N',N'-dimethyl-N-2-pyridylethylenediamine; N,N-Dimethyl-N'-benzyl-N'-(2-pyridyl)ethylenediamine; N,N-Dimethyl-N'-benzyl-N'-(alpha-pyridyl)ethylenediamine; N-Benzyl-N',N'-dimethyl-N-(2-pyridyl)ethylenediamine; N-Benzyl-N',N'-dimethyl-N-2-(pyridylethylene)diamine; N-Benzyl-N-(2-pyridyl)-N',N'-dimethyl ethylenediamine; N,N-Dimethyl-N'-benzyl-N'-(alpha.-pyridyl)ethylenediamine; N'-benzyl-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine; N,N-Dimethyl-N'-(phenylmethyl)-N'-2-pyridinyl-1,2-ethanediamine; N,N-dimethyl-N'-(phenylmethyl)-N'-pyridin-2-ylethane-1,2-diamine; N-Benzyl-N',N'-Dimethyl-N-Pyridin-2-Yl-Ethane-1,2-Diamine Hydrochloride; 1,2-Ethanediamine, N,N-dimethyl-N'-(phenylmethyl)-N'-2-pyridinyl-(9CI); 2-(Benzyl(2-dimethylaminoethyl)amino)pyridine; 2-(N-Benzyl-N-(2-dimethylaminoethyl)amino)pyridine; 2-(benzyl(2-(dimethylamino)ethyl)amino)pyridine; 2-[Benzyl(2-dimethylaminoethyl)amino]pyridine; 2-[N-Benzyl-N-(2-dimethylaminoethyl)amino]pyridine

Indication

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[1]
Hypersensitivity	4A80-4A85	Approved	[2]
Urticaria	EB00-EB05	Approved	[1]
Vasomotor/allergic rhinitis	CA08	Approved	[1]
Pruritus	EC90	Investigative	[1]

• Therapeutic Class: Antiallergic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 255.36
  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:
  Absorption: The drug is well absorbed in the digestive tract []
  Metabolism: The drug is metabolized via the hepatic []
• Chemical Identifiers:
  Formula: C16H21N3
  IUPAC Name: N'-benzyl-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine
  Canonical SMILES: CN(C)CCN(CC1=CC=CC=C1)C2=CC=CC=N2
  InChI: InChI=1S/C16H21N3/c1-18(2)12-13-19(16-10-6-7-11-17-16)14-15-8-4-3-5-9-15/h3-11H,12-14H2,1-2H3
  InChIKey: UFLGIAIHIAPJJC-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5587
  ChEBI ID: CHEBI:9741
  CAS Number: 91-81-6
  DrugBank ID: DB00792
  TTD ID: D0B4JQ
• 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	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Gene/Protein Processing	[4]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[5]

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

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Tripelennamine

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Mepyramine	DMB4SFH	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Mepyramine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[6]
Phenyltoloxamine	DMKAEQW	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Phenyltoloxamine.	Allergic/hypersensitivity disorder [4A80-4A8Z]	[6]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Memantine	DMD9WSC	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Memantine.	Alzheimer disease [8A20]	[7]
Rivastigmine	DMG629M	Moderate	Antagonize the effect of Tripelennamine when combined with Rivastigmine.	Alzheimer disease [8A20]	[8]
Donepezil	DMIYG7Z	Moderate	Antagonize the effect of Tripelennamine when combined with Donepezil.	Alzheimer disease [8A20]	[8]
Desipramine	DMT2FDC	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Desipramine.	Attention deficit hyperactivity disorder [6A05]	[7]
Cariprazine	DMJYDVK	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Cariprazine.	Bipolar disorder [6A60]	[7]
Loperamide	DMOJZQ9	Moderate	Additive antimotility effects by the combination of Tripelennamine and Loperamide.	Bowel habit change [ME05]	[9]
Acetylcholine	DMDF79Z	Moderate	Antagonize the effect of Tripelennamine when combined with Acetylcholine.	Cataract [9B10]	[10]
Umeclidinium	DM4E8O9	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Umeclidinium.	Chronic obstructive pulmonary disease [CA22]	[11]
Tiotropium	DMFDC0Q	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Tiotropium.	Chronic obstructive pulmonary disease [CA22]	[11]
Revefenacin	DMMP5SI	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Revefenacin.	Chronic obstructive pulmonary disease [CA22]	[11]
Ethanol	DMDRQZU	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Ethanol.	Cystitis [GC00]	[12]
Cyclobenzaprine	DM1YBRM	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Cyclobenzaprine.	Depression [6A70-6A7Z]	[7]
Isocarboxazid	DMAF1NB	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Isocarboxazid.	Depression [6A70-6A7Z]	[13]
OPC-34712	DMHG57U	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and OPC-34712.	Depression [6A70-6A7Z]	[7]
Clomipramine	DMINRKW	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Clomipramine.	Depression [6A70-6A7Z]	[7]
Doxepin	DMPI98T	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Doxepin.	Depression [6A70-6A7Z]	[7]
Maprotiline	DMPWB7T	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Maprotiline.	Depression [6A70-6A7Z]	[7]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Esketamine.	Depression [6A70-6A7Z]	[14]
Mepenzolate	DM8YU2F	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Mepenzolate.	Digestive system disease [DE2Z]	[6]
Oxybutynine	DMJPBAX	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Oxybutynine.	Discovery agent [N.A.]	[7]
Zonisamide	DM0DTF7	Major	Increased risk of hyperpyrexia by the combination of Tripelennamine and Zonisamide.	Epilepsy/seizure [8A61-8A6Z]	[15]
Diphenhydramine	DMKQTBA	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Diphenhydramine.	Episodic vestibular syndrome [AB31]	[7]
Solifenacin	DMG592Q	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Solifenacin.	Functional bladder disorder [GC50]	[7]
Tolterodine	DMSHPW8	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Tolterodine.	Functional bladder disorder [GC50]	[7]
Pilocarpine	DMV9ADG	Moderate	Antagonize the effect of Tripelennamine when combined with Pilocarpine.	Glaucoma [9C61]	[10]
Procarbazine	DMIK367	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Procarbazine.	Hodgkin lymphoma [2B30]	[13]
Belladonna	DM2RBWK	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Belladonna.	Infectious gastroenteritis/colitis [1A40]	[7]
Amantadine	DMS3YE9	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Amantadine.	Influenza [1E30-1E32]	[16]
ITI-007	DMUQ1DO	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and ITI-007.	Insomnia [7A00-7A0Z]	[7]
Dicyclomine	DMZSDGX	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Dicyclomine.	Irritable bowel syndrome [DD91]	[7]
Physostigmine	DM2N0TO	Moderate	Antagonize the effect of Tripelennamine when combined with Physostigmine.	Lips/oral mucosa miscellaneous disorder [DA02]	[8]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[17]
Flibanserin	DM70DTN	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Flibanserin.	Mood disorder [6A60-6E23]	[18]
Thalidomide	DM70BU5	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Thalidomide.	Multiple myeloma [2A83]	[12]
Dimenhydrinate	DM264B3	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Dimenhydrinate.	Nausea/vomiting [MD90]	[7]
Promethazine	DM6I5GR	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Promethazine.	Nausea/vomiting [MD90]	[7]
Apraclonidine	DMO4PVE	Moderate	Additive CNS depression effects by the combination of Tripelennamine and Apraclonidine.	Optic nerve disorder [9C40]	[19]
Flavoxate	DMKV4NL	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Flavoxate.	Pain [MG30-MG3Z]	[7]
Biperiden	DME78OA	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Biperiden.	Parkinsonism [8A00]	[6]
Orphenadrine	DMW542E	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Orphenadrine.	Parkinsonism [8A00]	[7]
Methylscopolamine	DM5VWOB	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Methylscopolamine.	Peptic ulcer [DA61]	[7]
Quetiapine	DM1N62C	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Quetiapine.	Schizophrenia [6A20]	[7]
Mesoridazine	DM2ZGAN	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Mesoridazine.	Schizophrenia [6A20]	[6]
Aripiprazole	DM3NUMH	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Aripiprazole.	Schizophrenia [6A20]	[7]
Iloperidone	DM6AUFY	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Iloperidone.	Schizophrenia [6A20]	[7]
Paliperidone	DM7NPJS	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Paliperidone.	Schizophrenia [6A20]	[7]
Perphenazine	DMA4MRX	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Perphenazine.	Schizophrenia [6A20]	[7]
Molindone	DMAH70G	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Molindone.	Schizophrenia [6A20]	[7]
Thiothixene	DMDINC4	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Thiothixene.	Schizophrenia [6A20]	[7]
Trifluoperazine	DMKBYWI	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Trifluoperazine.	Schizophrenia [6A20]	[7]
Asenapine	DMSQZE2	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Asenapine.	Schizophrenia [6A20]	[7]
Pimozide	DMW83TP	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Pimozide.	Schizophrenia [6A20]	[7]
Chlorpheniramine	DM5URA2	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Chlorpheniramine.	Vasomotor/allergic rhinitis [CA08]	[7]
Brompheniramine	DMFOVSD	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Brompheniramine.	Vasomotor/allergic rhinitis [CA08]	[7]
Acrivastine	DMTIGA0	Moderate	Additive anticholinergic effects by the combination of Tripelennamine and Acrivastine.	Vasomotor/allergic rhinitis [CA08]	[6]

References

• [1] Tripelennamine FDA Label
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Involvement of histamine H1 and H2 receptors in the regulation of STAT-1 phosphorylation: inverse agonism exhibited by the receptor antagonists. Int Immunopharmacol. 2005 Jul;5(7-8):1299-309.
• [4] Cholinesterase inhibition by phenothiazine and nonphenothiazine antihistaminics: analysis of its postulated role in synergizing organophosphate toxicity. Toxicol Appl Pharmacol. 1975 Feb;31(2):179-90.
• [5] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
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• [7] 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]
• [8] Beers MH, Ouslander JG, Rollingher I, Reuben DB, Brooks J, Beck JC "Explicit criteria for determining inappropriate medication use in nursing home residents." Arch Intern Med 151 (1991): 1825-32. [PMID: 1888249]
• [9] Eronen M, Putkonen H, Hallikainen T, Vartiainen H "Lethal gastroenteritis associated with clozapine and loperamide." Am J Psychiatry 160 (2003): 2242-2243. [PMID: 14638602]
• [10] Multum Information Services, Inc. Expert Review Panel.
• [11] 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]
• [12] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
• [13] Canadian Pharmacists Association.
• [14] Cerner Multum, Inc. "Australian Product Information.".
• [15] Product Information. Zonegran (zonisamide) Elan Pharmaceuticals, S. San Francisco, CA.
• [16] Postma JU, van Tilburg W "Visual hallucinations and delirium during treatment with amantadine (Symmetrel)." J Am Geriatr Soc 23 (1975): 212-5. [PMID: 123540]
• [17] Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
• [18] Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
• [19] Product Information. Alphagan (brimonidine ophthalmic). Allergan Inc, Irvine, CA.