Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an

antipruritic Antipruritics, abirritants, or anti-itch drugs, are medications that inhibit the itching (Latin: ''pruritus'') often associated with sunburns, allergic reactions, eczema, psoriasis, chickenpox, fungal infections, insect bites and stings like those ...

and first-generation antihistamine. It can be used in the treatment of asthma,

hay fever Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...

, rhinitis, and urticaria, but is now less common as it has been replaced by newer antihistamines. The drug was patented at CIBA, which merged with Geigy into Ciba-Geigy, and eventually becoming Novartis.

Medical uses

Where and when it is/was in common use, tripelennamine is used much like other mildly-anticholinergic antihistamines to treat conditions of the upper respiratory tract arising from illnesses and hay fever. It can be used alone or in combination with other agents to have the desired effect. Cough medicines of the general formula tripelennamine + codeine/dihydrocodine/hydrocodone ± expectorant ± decongestant(s) are popular where available. Among these are the Pyribenzamine cough syrups which contain codeine, with and without decongestants, listed in the 1978 ''Physicians' Desk Reference''; the codeine-tripelennamine synergy is well-known and makes such mixtures more useful for their intended purposes.

Side effects

Tripelennamine is mildly

sedating Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

. Other side effects can include irritation, dry mouth, nausea, and dizziness. A large study on people 65 years old or older linked the development of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

and other forms of dementia to the "higher cumulative" use of first-generation antihistamines, due to their anticholinergic properties.

Pharmacology

Pharmacodynamics

Tripelennamine acts primarily as an antihistamine, or H₁

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

. It has little to no anticholinergic activity, with 180-fold

selectivity Selectivity may refer to: Psychology and behaviour * Choice, making a selection among options * Discrimination, the ability to recognize differences * Socioemotional selectivity theory, in social psychology Engineering * Selectivity (radio), a ...

for the H₁ receptor over the muscarinic acetylcholine receptors (for comparison, diphenhydramine had 20-fold selectivity for the H₁ receptor). In addition to its antihistamine properties, tripelennamine also acts as a weak serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).

Pharmacokinetics

The elimination half-life of tripelennamine is 4 to 6 hours. In a clinical study, the half-life of tripelennamine following

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

of 50 to 100 mg was 2.9 to 4.4 hours.

History

Tripelennamine was first synthesized in 1946 by

Carl Djerassi Carl Djerassi (October 29, 1923 – January 30, 2015) was an Austrian-born Bulgarian-American pharmaceutical chemist, novelist, playwright and co-founder of Djerassi Resident Artists Program with Diane Middlebrook, Diane Wood Middlebrook. He is b ...

, working in the laboratory of Charles Huttrer at CIBA, shortly after Djerassi got his

B.S BS, B.S., Bs or bs may refer to: Arts and entertainment *BS-, a prefix for all games broadcast for the Satellaview modem via the Japanese Broadcasting Satellite system * "B.S." (song), a song by Jhené Aiko from the album ''Chilombo'' *Team BS, ...

. It was his first patent.

Society and culture

Availability

Tripelennamine is no longer available in the United States.

References

{{Monoamine reuptake inhibitors Aminopyridines CYP2D6 inhibitors H1 receptor antagonists Serotonin–norepinephrine–dopamine reuptake inhibitors