Introduction

Pheniramine is a first-generation antihistamine in the

alkylamine class, similar to brompheniramine and
chlorpheniramine. 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.

Brand Names:
Naphcon A, Opcon-A, Robitussin AC, Visine-A

Generic Name:
Pheniramine
 Structure

Weight
Average: 240.3434
Monoisotopic: 240.16264865

Chemical Formula
C16H20N2

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.
 Mechanism of action
Pheniramine competes with histamine for the histamine H1
receptor, acting as an inverse agonist once bound. 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. 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.
The binding of pheniramine to H4 receptors, and subsequent
inverse agonism, may also contribute to reduced itching by
antagonizing inflammation.

TARGETS

1. Histamine H4 Receptor :
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...

Molecular Weight: 44495.375 Da

2. Histamine H1 Receptor:

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.

Molecular Weight: 55783.61 Da

3. Nuclear receptor subfamily 1 group 1 member 3:

Histamine H1 Receptor:

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...

Molecular Weight: 39942.145 Da

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.

Metabolism:

Pheniramine undergoes N-dealkylation to N-

didesmethylpheniramine and N-desmethylpheniramine.
Hover over products below to view reaction partners
 Pheniramine
o N-desmethylpheniramine
 N-didesmethylpheniramine
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.

Toxicity
Case reports involving pheniramine overdosage mention the
rare possibility of arrythmias, cutaneous eruptions, and
rhabdomyolysis with acute kidney injury.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.

Conclusion
 Pheniramine is taken in overdose more frequently than other
antihistamines relative to its market share. It is also more
likely to be abused than other antihistamines. In overdose, it
appears to be more proconvulsant than other antihistamines.

The End