Samantha Westhorpe and Natalie Mar

Chemical Structure of Histamine taken from Wikipedia 5/4/09


Histamine is a chemical substance that was first isolated from ergot in 1910 by Sir Henry Dale at Wellcome Laboratories. Dale first began working with ergot at the suggestion of laboratory founder, Henry Wellcome. Ergot is a "parasitic fungus that infects rye and other cereal grasses" (Simmons 237). By 1910, Dale discovered that histamine was a type of stimulant that was being released from the fungus. He then found that histamine can be found in almost all the cells of the body and that it serves as an inflammatory response. (Simmons 236-238)

Histamine - What is it?

  1. A protein, which, when released, "increases the permeability and distension of blood capillaries, resulting in edema and erythema" (Tortora 552).
  2. A chemical containing an amine group, that is released by damaged cells in response to an injury.
Picture taken from

What Causes Histamines to be Released?
IgE antibodies are released from specialized B cells in response to an antigen such as pollen. The IgE antibodies then bind to specific receptors on the surfaces of cells like mast cells and basophils. (Tortora) These cells are filled with granules containing chemical mediators--HISTAMINES! The histamines and other chemical mediators are released from the mast cells when the allergen comes in contact with the mast cell, generating an allergic reaction.

Histamine Receptors:
Histamine is only able to bind to specific receptors. The four major histamine receptors and their key characteristics are outlined in the table below.
H1 Receptor
H2 Receptor
H3 Receptor
H4 Receptor
Receptor Expression
Widespread; eg: neurons and smooth muscles
Widespread; eg: smooth muscles and the heart
High expression in bone marrow and peripheral hematopoietic cells
High expression in bone marrow and peripheral hematopoietic cells
General Histamine Function
Increased pain, vasodilation, vascular permeability, hypertension, tachycardia, headache, bronchoconstriction, etc.
Increased gastric acid secretion, vascular permeability, tachycardia, bronchodilation, headache, mucus production, etc.
Prevents excessive bronchoconstriction; no mast-cell involvement
Differentiation of myeloblasts and promyelocytes
Histamine Function in Allergic & Immune Modulation
Increased release of histamine and other chemical mediators; increased cellular adhesion-molecule expression & chemotaxis of eosinophils and neutrophils; blocking of humoral immunity & IgE production
Decreased eosinophil & neutrophil chemotaxis; induction of humoral immunity; suppression of cellular immunity; indirect role in allergy, autoimmunity, malignant disease, etc,
Possibly involved in control of neurogenic inflammation through local neuron-mast-cell feedback loops; pro-inflammatory activity activity
Increased cytosolic calcium in human eosinophils; increased eosinophil chemotaxis, etc.
Histamine Function in the CNS
Cycle of sleeping & waking, food intake, thermal regulation, emotions/aggression, locomotion, memory, learning
Presynaptic heteroreceptor; decreased histamine, dopamine, serotonin, noradrenaline, and acetylcholine release

__Samantha's Case Study: Histamines in our Lungs__
Typical symptoms of an upper respiratory allergy:
  • Itchy and teary eyes
  • Congested nasal passages
  • Coughing
  • Sneezing
These symptoms are usually treated with anti-histamine drugs that compete for histamine receptor sites.


In response to a typical allergic reaction mast cells and basophils release histamine, a mediator chemical. While the histamine response is a normal response to an allergic stimulus, the reaction can interfere with people’s daily lives. The release of histamine may cause swelling, redness, increased mucus secretion and smooth muscle contraction, which can result in difficulty breathing. (Tortora 552). To overcome these symptoms many people turn toward anti-histamine medications. What many people don’t know is what histamines do. We are going to explore is the history of antihistamines, how they work, and the advantages and risks of using them today.

Antihistamine- What is it?

Antihistamines are chemical drugs taken in order to reduce symptoms of an allergic reaction. Antihistamines are inverse agonists for the H1 receptor, blocking the ability of histamine to be released from mast cells and basophils, therefore decreasing the incidence of symptoms caused by the histamine response. Antihistamines also work to prevent histamine from binding to the outside of cells. Common Allergic reactions include allergic rhinoconjuctivitis (ex.seasonal allergies, hay fever, itchy watery eyes) and urticaria (ex. hives, red, itchy bumps on skin). Over 40 different antihistamine drugs are used world wide; they are also one of the most commonly used drugs in the world. (Simons).

When was Antihistamine first Discovered?

The first antihistamine was discovered in 1937 by Bovet and Staub at the Institute Pastuer. (Howarth). Clinical usage of antihistamines began after World War II around 1942. (De Vos). Although the early drugs did improve symptoms of allergic rhinitis ans urticaria they had problems in specificity. The drugs caused many side effects such as surpressing not only histamine but choline, seratonin, and dopamine. (Howarth). There is still ongoing research in targeting receptors. Recent research has discovered 4 different histamine receptors (H1, H2, H3, H4) that cause different responses in the body. In the development of antihistamines there is a search to create medications that block each one. Currently there are antihistamines that target H1 and H2 receptors. (Simons).


What is the Difference Between First and Second Generation Antihistamines?

First generation Antihistamines typically have a stronger sedative effect due to the fact that they can pass through the blood-brain barrier. (Bachert) First generation antihistamines have a low molecular weight and are non-specific, meaning they can interfere with other neurotransmitters such as choline, seratonin and dopamine. (Simons). A common first generation antihistamine that is widely used today is diphenhydramine also known as Benadryl. First generation drugs are known to be toxic when taken in high doses. (Simons). Many of the second generation antihistamines have been derived from existing medications. They are similar compounds but are able to target H1 receptors better, therefore increasing selectivity. Second generation antihistamines are known to not cause drowziness; this is becaue of their inability to cross the blood-brain barrier. A common second generation is Cetirzine which in marketed as Zyrtec. Zyrtec has become quite popular because it does not cause sedation. Although leaps have been made in improving antihistamine medications, they are not without side effects.

A Sample Second Generation Antihistamine found on

Are Antihistamines Affective in Treating the Symptoms of Allergic Rhinitis and/or Urticaria?

In treating acute urticaria, H1 antihistamines have been proven to "reduce the number, size, and duration of wheals and decrease itching." (Simons). Patients with chronic urticaria have a variety of options for treatment. No treatment has been studied enough to be better than the other. Some patients use only first generation, others uses only second generation, while others find a combination of both ( second generation during the day, first generation at night) to work best. Still other treatment options are being researched for chronic urticaria such as using H2 and H1 antihistamines. The choice of medication application weather oral or topical is also of concern to the patient. Seasonal allergy suffers appear to have all symptoms reduced after using H1 antihistamines. Research on first generation antihistamines has not been performed appropriately for today's standards (ex. randomization, double-blind, placebos) but second generation antihistamines have been shown to work well in research studies.(Simons). Once again the decision on which medication to use is left into the hands of the doctor and patient. Allergic Rhinitis can be treated with oral or topical H1 antihistamines.

Pro and Cons of taking H1-Antihistamines (Simons)

Benefits of Antihistamines
Negative Effects of Antihistamines
Decreased allergic inflammation, itching, sneezing, rhinorrhea, and whealing
Decreased neurotransmission in CNS
Decreased mediator (histamine release)
Increased sedation
Decreased antigen presentation, chemotaxis and proinflammatory cytokines
Decreased cognitive and psychomotor performance

Increased appetite

Increased dry mouth

hypotension, dizziness, reflex tachycardia

prolonged QT intervals, may result in ventricular arrhythmias
(more common in women and those with compromised organs)

How Do First Generation Antihistamines Affect Alertness?

It is of common knowledge that taking antihistamines can make people very tired and unable to focus during the day. This is due to the fact that these drugs, like Benadryl, can cross the blood-brain barrier and affect the processes of many neurotransmitters due to the drug's lack of specificty. First generation antihistamines depress the central nervous system proceses causing sedation. In a randomized study by JM Wieler et al, "a 50mg dose of diphenhydramine (Benadryl) impared driving performance to a greater extent than alcohol; the alcohol dose produced an estimated blood alcohol concentration of 0.1 percent." (Simons)

Works Cited

Alvarez, Edgardo O. "The Role of Histamine on Cognition." 13 Dec. 2008. Behavioral Brain Research. Science Direct.

Bachert. 1998. Histamine- A Major role in allergy? . Clinical and Experimental Allergy. 28: 15-19.

Caughey, G. "WBC in Lung Produces Histamine: Study" 13 Jan. 2007. University of California, San Francisco. Bio-Medicine. (2003-2009)

De Vos, Christine. "New Antihistamines." Clinical and Experimental Allergy 19 (1989): 503-07.

Howarth, P. H. "Assessment of antihistamine efficacy and potency." Clinical and Experimental Allergy 29 (1999): 87-97.

Simmons, J. Doctors and Discoveries. Boston: Houghton Mifflin Company, 1949. (236-240)

Simons, F. Estelle R. 2004. Advances in H1-Antihistamines. New England Journal of Medicine. 351: 2203-2217

Tortora, Gerard J., Berdell R. Funke, and Christine L. Case. Microbiology An Introduction with CDROM. 9th ed. Boston: Benjamin-Cummings Company, 2006.

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