Identification

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Name
Pheniramine
Accession Number
DB01620
Type
Small Molecule
Groups
Approved
Description

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 [cetirazine] and [loratidine].

Structure
Thumb
Synonyms
  • Feniramina
  • Pheniramine
  • Pheniraminum
Product Ingredients
IngredientUNIICASInChI Key
Pheniramine maleateNYW905655B132-20-7SSOXZAQUVINQSA-BTJKTKAUSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Allergy Eye DropsPheniramine maleate (3 mg/1mL) + Naphazoline hydrochloride (0.25 mg/1mL)Solution / dropsOphthalmicChain Drug Consortium2014-01-10Not applicableUs
Allergy Eye DropsPheniramine maleate (0.315 %) + Naphazoline hydrochloride (0.02675 %)Solution / dropsOphthalmicBausch & Lomb Inc2013-02-272017-08-03Canada
Allergy Eye DropsPheniramine maleate (3 mg/1mL) + Naphazoline hydrochloride (0.25 mg/1mL)Solution / dropsOphthalmicCVS Health2013-01-25Not applicableUs
Antitussive Decong Antihistamine SyrPheniramine maleate (6.5 mg) + Dextromethorphan hydrobromide (15 mg) + Mepyramine maleate (6.5 mg) + Phenylpropanolamine hydrochloride (13 mg)SyrupOralProdemdis Enr.1992-12-312001-04-26Canada
Bronchodex D CapPheniramine maleate (12.5 mg) + Chlorpheniramine maleate (1 mg) + Phenylpropanolamine hydrochloride (50 mg)Capsule, extended releaseOralProdemdis Enr.1981-12-312001-04-26Canada
Bronchodex PediatriquePheniramine maleate (5 mg) + Dextromethorphan hydrobromide (5 mg) + Guaifenesin (50 mg) + Pseudoephedrine hydrochloride (15 mg)SyrupOralTherapex Division De E Z Em Canada Inc1983-12-311997-07-22Canada
Bronchosirum Pour EnfantsPheniramine maleate (6.25 mg) + Dextromethorphan hydrobromide (15 mg) + Mepyramine maleate (6.25 mg) + Phenylpropanolamine hydrochloride (12.5 mg)SyrupOralBronchosirum Inc.1987-12-311997-08-05Canada
Caldomine Dh AdultePheniramine maleate (12.5 mg) + Hydrocodone bitartrate (5 mg) + Mepyramine maleate (12.5 mg) + Phenylpropanolamine hydrochloride (25 mg)LiquidOralTechnilab Pharma Inc.1981-12-312001-04-04Canada
Caldomine Dh EnfantPheniramine maleate (6.25 mg) + Hydrocodone bitartrate (1.667 mg) + Mepyramine maleate (6.25 mg) + Phenylpropanolamine hydrochloride (12.5 mg)LiquidOralTechnilab Pharma Inc.1982-12-312001-04-04Canada
Calmylin AcePheniramine maleate (7.5 mg) + Codeine phosphate (10 mg) + Guaifenesin (100 mg)SyrupOralTEVA Canada Limited1996-12-31Not applicableCanada
International/Other Brands
AVIL
Categories
UNII
134FM9ZZ6M
CAS number
86-21-5
Weight
Average: 240.3434
Monoisotopic: 240.16264865
Chemical Formula
C16H20N2
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

Pharmacology

Indication

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

Associated Conditions
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 H1 receptor
inverse agonist
Humans
UNuclear receptor subfamily 1 group I member 3Not AvailableHumans
AHistamine H4 receptor
inverse agonist
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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

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
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

Affected organisms
  • Humans and other mammals
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
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Pheniramine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Pheniramine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Pheniramine.
AbexinostatThe risk or severity of QTc prolongation can be increased when Pheniramine is combined with Abexinostat.
AcebutololThe risk or severity of QTc prolongation can be increased when Pheniramine is combined with Acebutolol.
AceprometazineThe risk or severity of QTc prolongation can be increased when Pheniramine is combined with Aceprometazine.
AcetyldigoxinThe risk or severity of QTc prolongation can be increased when Pheniramine is combined with Acetyldigoxin.
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.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

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. [PubMed:9795048]
  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. [PubMed:22918191]
  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. [PubMed:4385103]
  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. [PubMed:3988394]
  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. [PubMed:25948974]
  6. Bobik A, McLean AJ: Cardiovascular complications due to pheniramine overdosage. Aust N Z J Med. 1976 Feb;6(1):65-7. [PubMed:1065303]
  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). [PubMed:30142724]
  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. [PubMed:679637]
  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]
External Links
Human Metabolome Database
HMDB0015557
PubChem Compound
4761
PubChem Substance
46505932
ChemSpider
4597
BindingDB
50017656
ChEBI
91591
ChEMBL
CHEMBL1193
Therapeutic Targets Database
DAP001063
PharmGKB
PA164744506
Wikipedia
Pheniramine
ATC Codes
R06AB05 — PheniramineD04AA16 — Pheniramine
FDA label
Download (852 KB)
MSDS
Download (116 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentAllergic Disorder of Respiratory System / Cold / Flu caused by Influenza1
3WithdrawnTreatmentRespiratory Tract Infections (RTI)1
4Unknown StatusTreatmentConjunctivitis, Seasonal Allergic1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Capsule, extended releaseOral
SprayNasal
Powder, for suspensionOral
Kit; powderOral
Solution / dropsOphthalmic
SolutionOphthalmic
SyrupOral
LiquidOral
PowderOral
Powder, for solutionOral
Granule, for solutionOral
Tablet, extended releaseOral
SuspensionOral
TabletOral
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
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

Taxonomy

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
Pheniramine / Aralkylamine / Benzenoid / Monocyclic benzene moiety / Heteroaromatic compound / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

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. [PubMed:17016423]
  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. [PubMed:2567596]
  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. [PubMed:7714410]
  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. [PubMed:11526976]
  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. [PubMed:8835636]
  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. [PubMed:20027159]
  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. [PubMed:14506317]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
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. [PubMed:20869355]
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. [PubMed:22918191]

Drug created on August 29, 2007 14:15 / Updated on November 02, 2019 04:27