Pheniramine

Identification

Summary

Pheniramine is an antihistamine used to treat allergic rhinitis and pruritus.

Brand Names
Naphcon A, Opcon-A, Visine-A
Generic Name
Pheniramine
DrugBank Accession Number
DB01620
Background

Pheniramine is a first-generation antihistamine in the alkylamine class, similar to brompheniramine and chlorpheniramine.3 It is used in some over-the-counter allergy as well as cold & flu products in combination with other drugs. Pheniramine's use as an anti-allergy medication has largely been supplanted by second-generation antihistamines such as cetirizine and loratadine.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 240.3434
Monoisotopic: 240.16264865
Chemical Formula
C16H20N2
Synonyms
  • Feniramina
  • Pheniramine
  • Pheniraminum

Pharmacology

Indication

Pheniramine is commonly used in over-the-counter products to treat seasonal allergies or cold and flu symptoms.10,11

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination for symptomatic treatment ofAllergic conjunctivitisCombination Product in combination with: Naphazoline (DB06711)••• •••••••••••••
Symptomatic treatment ofAllergic skin reaction••••••••••••
Treatment ofAllergic urticaria•••••••••••••••••••••• •••••••••• ••••••••• •••••• ••••••
Treatment ofAnaphylaxis•••••••••••••••••••••• •••••••••• ••••••••• •••••• ••••••
Treatment ofAngioedema•••••••••••••••••••••• •••••••••• ••••••••• •••••• ••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Pheniramine acts as an antagonist to allergic symptoms stemming from inappropriate histamine release to reduce edema, itching, and redness. The same antihistamine effect also produces sedation by acting in the central nervous system.1,9

Mechanism of action

Pheniramine competes with histamine for the histamine H1 receptor, acting as an inverse agonist once bound.1 The reduction in H1 receptor activity is responsible for reduced itching as well as reduced vasodilation and capillary leakage leading to less redness and edema.9 This can be seen in the suppression of the histamine-induced wheal (swelling) and flare (vasodilation) response. Inverse agonism of the H1 receptor in the CNS is also responsible for the sedation produced by first-generation antihistamines like pheniramine.9 The binding of pheniramine to H4 receptors, and subsequent inverse agonism, may also contribute to reduced itching by antagonizing inflammation.2

TargetActionsOrganism
AHistamine H4 receptor
inverse agonist
Humans
AHistamine H1 receptor
inverse agonist
Humans
UNuclear receptor subfamily 1 group I member 3Not AvailableHumans
Absorption

The administration of 30.5 mg of free base pheniramine resulted in a Cmax of 173-294 ng/L with a Tmax of 1-2.5 h.4

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Pheniramine undergoes N-dealkylation to N-didesmethylpheniramine and N-desmethylpheniramine.3

Hover over products below to view reaction partners

Route of elimination

Pheniramine is eliminated by metabolism and via renal excretion.3 24.3% of pheniramine is present in the urine as the parent drug.

Half-life

The terminal half-life of pheniramine administered via IV is 8-17 h.4

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Case reports involving pheniramine overdosage mention the rare possibility of arrythmias, cutaneous eruptions, and rhabdomyolysis with acute kidney injury.5,6,7 The administration of activated charcoal effectively prevents the absorption of pheniramine as it largely adsorbs to the charcoal, therefore this may be of benefit in cases of overdose if provided early after ingestion.8

Pathways
PathwayCategory
Pheniramine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcrivastineThe risk or severity of QTc prolongation can be increased when Pheniramine is combined with Acrivastine.
AdenosineThe risk or severity of QTc prolongation can be increased when Pheniramine is combined with Adenosine.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Pheniramine.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Pheniramine.
AlimemazineThe risk or severity of QTc prolongation can be increased when Alimemazine is combined with Pheniramine.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Pheniramine maleateNYW905655B132-20-7SSOXZAQUVINQSA-BTJKTKAUSA-N
International/Other Brands
AVIL
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Alahist DPheniramine maleate (17.5 mg/1) + Phenylephrine hydrochloride (10 mg/1)TabletOralPoly Pharmaceuticals, Inc.2020-04-01Not applicableUS flag
Alahist DMPheniramine maleate (12.5 mg/5mL) + Dextromethorphan hydrobromide monohydrate (10 mg/5mL) + Phenylephrine hydrochloride (5 mg/5mL)LiquidOralPoly Pharmaceuticals, Inc.2023-06-08Not applicableUS flag
Allergy Eye DropsPheniramine maleate (3 mg/1mL) + Naphazoline hydrochloride (0.25 mg/1mL)Solution / dropsOphthalmicCVS Health2013-01-25Not applicableUS flag
Allergy Eye DropsPheniramine maleate (3 mg/1mL) + Naphazoline hydrochloride (0.25 mg/1mL)Solution / dropsOphthalmicChain Drug Consortium2014-01-10Not applicableUS flag
Allergy Eye DropsPheniramine maleate (0.315 % w/v) + Naphazoline hydrochloride (0.02675 % w/v)Solution / dropsOphthalmicBausch & Lomb Inc2013-02-272017-08-03Canada flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Alahist DPheniramine maleate (17.5 mg/1) + Phenylephrine hydrochloride (10 mg/1)TabletOralPoly Pharmaceuticals, Inc.2020-04-01Not applicableUS flag
Alahist DMPheniramine maleate (12.5 mg/5mL) + Dextromethorphan hydrobromide monohydrate (10 mg/5mL) + Phenylephrine hydrochloride (5 mg/5mL)LiquidOralPoly Pharmaceuticals, Inc.2023-06-08Not applicableUS flag
FENAMED 45,5 MG/2 ML IM/IV ENJ. COZ. ICEREN 50 AMPULPheniramine (45.5 mg/2ml)InjectionIntramuscular; IntravenousAVİCENNA FARMA DIŞ TİC. VE PAZ. A.Ş.2019-11-26Not applicableTurkey flag

Categories

ATC Codes
R06AB05 — PheniramineD04AA16 — Pheniramine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pheniramines. These are compounds containing a pheniramine moiety, which is structurally characterized by the presence of a 2-benzylpyridine linked to an dimethyl(propyl)amine to form a dimethyl[3-phenyl-3-(pyridin-2-yl)propyl]amine skeleton.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pheniramines
Direct Parent
Pheniramines
Alternative Parents
Aralkylamines / Benzene and substituted derivatives / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amine / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Heteroaromatic compound / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organonitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
134FM9ZZ6M
CAS number
86-21-5
InChI Key
IJHNSHDBIRRJRN-UHFFFAOYSA-N
InChI
InChI=1S/C16H20N2/c1-18(2)13-11-15(14-8-4-3-5-9-14)16-10-6-7-12-17-16/h3-10,12,15H,11,13H2,1-2H3
IUPAC Name
dimethyl[3-phenyl-3-(pyridin-2-yl)propyl]amine
SMILES
CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=N1

References

General References
  1. Schulze FR, Buschauer A, Schunack W: Combined histamine H1/H2 receptor antagonists: part I. Pharmacological hybrids with pheniramine- and roxatidine-like substructures. Eur J Pharm Sci. 1998 Jul;6(3):177-86. [Article]
  2. Wade L, Bielory L, Rudner S: Ophthalmic antihistamines and H1-H4 receptors. Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):510-6. doi: 10.1097/ACI.0b013e328357d3ba. [Article]
  3. Kabasakalian P, Taggart M, Townley E: Urinary excretion of pheniramine and its N-demthylated metabolites in man--comparison with chlorpheniramine and brompheniramine data. J Pharm Sci. 1968 Apr;57(4):621-3. doi: 10.1002/jps.2600570416. [Article]
  4. Witte PU, Irmisch R, Hajdu P: Pharmacokinetics of pheniramine (Avil) and metabolites in healthy subjects after oral and intravenous administration. Int J Clin Pharmacol Ther Toxicol. 1985 Jan;23(1):59-62. [Article]
  5. Venugopal K, Reddy MM, Bharathraj MY, Jaligidad K, Kushal DP: Pheniramine Maleate-Induced Rhabdomyolysis and Aki: Is it Fatal? Toxicol Int. 2014 Sep-Dec;21(3):319-21. doi: 10.4103/0971-6580.155384. [Article]
  6. Bobik A, McLean AJ: Cardiovascular complications due to pheniramine overdosage. Aust N Z J Med. 1976 Feb;6(1):65-7. [Article]
  7. Gupta A, Arora P, Malhotra P, Sardana K: Pheniramine maleate: an apparently safe drug causing bullous fixed drug eruption. Dermatol Online J. 2018 Aug 23;24(6). [Article]
  8. Boehm JJ, Brown TC, Oppenheim RC: Reduction of pheniramine toxicity using activated charcoal. Clin Toxicol. 1978;12(5):523-30. doi: 10.3109/15563657809150026. [Article]
  9. Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
  10. Pheniramine/Naphazoline Eye Drop Monograph [Link]
  11. Acetaminophen/Pheniramine/Phenylephrine Solution Monograph [Link]
  12. Cameo Chemicals: Pheniramine maleate [Link]
Human Metabolome Database
HMDB0015557
PubChem Compound
4761
PubChem Substance
46505932
ChemSpider
4597
BindingDB
50017656
RxNav
8132
ChEBI
91591
ChEMBL
CHEMBL1193
Therapeutic Targets Database
DAP001063
PharmGKB
PA164744506
Wikipedia
Pheniramine
FDA label
Download (852 KB)
MSDS
Download (116 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Unknown StatusTreatmentAllergic Conjunctivitis (AC)1
3CompletedTreatmentAllergic Disorder of Respiratory System / Cold / Flu caused by Influenza1
3WithdrawnTreatmentRespiratory Tract Infections (RTI)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
Injection, solutionIntravenous45.5 g
Injection, solutionIntravenous
TabletOral25 MG
OintmentTopical1.25 %
SyrupOral15 mg/5ml
TabletOral22.7 mg
InjectionIntramuscular; Intravenous45.5 mg/2ml
Capsule, extended releaseOral
SprayNasal
Powder, for suspensionOral
Kit; powderOral
Injection, solutionIntramuscular; Intravenous
TabletOral
Injection, solutionIntramuscular; Intravenous45.5 mg/2ml
Solution / dropsOphthalmic
SolutionOphthalmic
SolutionOphthalmic0.25 mg/ml
SolutionConjunctival; Ophthalmic
SyrupOral
LiquidOral
Solution / dropsConjunctival
GranuleOral
PowderOral
Powder, for solutionOral
Granule, for solutionOral
Tablet, extended releaseOral
SuspensionOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)107Cameo Chemicals
boiling point (°C)181 °C at 1.30E+01 mm HgPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.377 mg/mLALOGPS
logP2.85ALOGPS
logP2.98Chemaxon
logS-2.8ALOGPS
pKa (Strongest Basic)9.48Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area16.13 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity76.05 m3·mol-1Chemaxon
Polarizability28.41 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9719
Blood Brain Barrier+0.9657
Caco-2 permeable+0.9034
P-glycoprotein substrateSubstrate0.6248
P-glycoprotein inhibitor INon-inhibitor0.9048
P-glycoprotein inhibitor IINon-inhibitor0.966
Renal organic cation transporterInhibitor0.7942
CYP450 2C9 substrateNon-substrate0.7957
CYP450 2D6 substrateSubstrate0.7888
CYP450 3A4 substrateSubstrate0.5421
CYP450 1A2 substrateNon-inhibitor0.9442
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.5302
CYP450 2C19 inhibitorNon-inhibitor0.7433
CYP450 3A4 inhibitorNon-inhibitor0.9034
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9161
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9375
BiodegradationNot ready biodegradable0.9876
Rat acute toxicity2.9748 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9031
hERG inhibition (predictor II)Non-inhibitor0.516
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-066r-7910000000-96eb6f4bb716d4764770
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0920000000-fd728bb396d025cac3f0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-7af6ac1b513c7f2f33a9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-ea7e67a76460b33d8306
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-f5daabe4b8aedf8605e6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014j-0900000000-4ccd8055b59ae6eabc90
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-1900000000-deb31ec7e47ca6a0e3ff
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-1900000000-add8b8849c3db116e181
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-2900000000-c38a45f14fb4ab5b1687
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014r-3900000000-1f2c04e07e8c46a0c722
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0910000000-549410c48d9c44650beb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-669fdf1a00514df13bf2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-59e6f9e272a364ed620a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-a9b1b534a7a36bdaf014
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-0d3c0ba161b03c4cc7d5
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0090000000-411cb761b4cdefd608e9
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-032a6dae54ee28d0a071
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-006x-9580000000-51bde137033a1637bed7
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00ku-7970000000-f137893be2c886b873cc
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0fr6-7910000000-57f9211cecf2287078c6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kf-5910000000-1f6ca78751bb6657af11
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-168.9531687
predicted
DarkChem Lite v0.1.0
[M-H]-149.86632
predicted
DeepCCS 1.0 (2019)
[M+H]+169.7823687
predicted
DarkChem Lite v0.1.0
[M+H]+152.22432
predicted
DeepCCS 1.0 (2019)
[M+Na]+169.5487687
predicted
DarkChem Lite v0.1.0
[M+Na]+158.31746
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inverse agonist
General Function
Histamine receptor activity
Specific Function
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agoni...
Gene Name
HRH4
Uniprot ID
Q9H3N8
Uniprot Name
Histamine H4 receptor
Molecular Weight
44495.375 Da
References
  1. Wade L, Bielory L, Rudner S: Ophthalmic antihistamines and H1-H4 receptors. Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):510-6. doi: 10.1097/ACI.0b013e328357d3ba. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inverse agonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  2. Leurs R, Bast A, Timmerman H: High affinity, saturable [3H]mepyramine binding sites on rat liver plasma membrane do not represent histamine H1-receptors. A warning. Biochem Pharmacol. 1989 Jul 1;38(13):2175-80. [Article]
  3. Yanni JM, Stephens DJ, Parnell DW, Spellman JM: Preclinical efficacy of emedastine, a potent, selective histamine H1 antagonist for topical ocular use. J Ocul Pharmacol. 1994 Winter;10(4):665-75. [Article]
  4. Nath C, Gupta MB: Role of central histaminergic system in lorazepam withdrawal syndrome in rats. Pharmacol Biochem Behav. 2001 Apr;68(4):777-82. [Article]
  5. Karadag CH, Ulugol A, Dokmeci D, Dokmeci I: The role of histamine H1-receptors in the anticonvulsive effect of morphine against maximal electroconvulsive shock in mice. Jpn J Pharmacol. 1996 Jun;71(2):109-12. [Article]
  6. Nosal R, Drabikova K, Jancinova V, Moravcova J, Lojek A, Ciz M, Macickova T, Pecivova J: H1-antihistamines and oxidative burst of professional phagocytes. Neuro Endocrinol Lett. 2009;30 Suppl 1:133-6. [Article]
  7. Gepdiremen A, Buyukokuroglu ME, Hacimuftuoglu A, Suleyman H: Contribution of the histaminergic receptor subtypes to histamine-induced cerebellar granular neurotoxicity. Pol J Pharmacol. 2003 May-Jun;55(3):383-8. [Article]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
Agonist at the canonical form of the receptor. Likely an antagonist at isoform 3 of the receptor.
General Function
Zinc ion binding
Specific Function
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name
NR1I3
Uniprot ID
Q14994
Uniprot Name
Nuclear receptor subfamily 1 group I member 3
Molecular Weight
39942.145 Da
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [Article]

Drug created at August 29, 2007 20:15 / Updated at February 02, 2024 22:54