Antihistamines (under construction)

Antihistamines (under construction)

The antihistamines recommended for or prescribed to treat allergic reactions, occasional insomnia, motion sickness or vertigo, and nausea and vomiting target histamine H1 receptors on mast cells, smooth muscle, endothelium, and in the brain’s tuberomammillary nucleus (a structure of histamine-releasing neurons in the posterior third of the hypothalamus involved in regulating arousal, learning, memory, sleep and energy balance). Antihistamine drugs act mechanistically as receptor antagonists or inverse agonists. The only clinically used inverse agonists are cetirizine, desloratadine and pyrilamine (a.k.a. mepyramine maleate- available OTC in British pharmacies). All first-generation antihistamines cause sedation: alimemazine tartrate and promethazine are highly sedating compared to chlorphenamine maleate and cyclizine which are less sedating. Newer second- or third-generation antihistamines with reduced ability to cross the blood brain barrier are classified as ‘non-sedating’.

All antihistamines have potential efficacy for reducing rhinorrhoea and sneezing associated with allergic rhinoconjunctivitis, and may be of some use in treating vasomotor rhinitis. Topically applied antihistamines are used in the eye, nose and on the skin. Oral antihistamines are effective in preventing urticaria, being used to treat urticarial rashes, pruritus, and insect bites/stings. Antihistamines are also used to manage drug allergies, and chlorphenamine maleate or promethazine hydrochloride injections are used along with adrenaline in emergency medicine to treat anaphylaxis and angioedema.

Some antihistamines are porphyrinogenic, so should be avoided in patients with acute porphyrias: alimemazine, chlorphenamine, desloratadine, fexofenadine, ketotifen, loratadine, and promethazine are considered to be safe in these patients.

Non-immune uses of H1 antihistamines (e.g. anti-emetic, and anti-insomnia use) and H2 receptor antagonists are discussed elsewhere.


The majority of antihistamines are available from a pharmacy without prescription. Some common examples are highlighted in the following sections.


Sedating antihistamines: the sedating effect of this group of antihistamines can be beneficial for patients whose sleep is disturbed by their symptoms.

Alimemazine tartrate is given orally to treat urticaria and pruritus.

Chlorphenamine maleate can be given to children >1 year old at recommended doses. It is used to provide symptomatic relief from allergies, including hay fever, urticaria, food allergy and drug reactions, as well as from the itch associated with chickenpox. Also used i.m. or i.v. in the emergency treatment of anaphylactic reactions.

Clemastine provides symptomatic relief from allergy. Note that it exhibits significant antimuscarinic activity.

Promethazine teoclate/hydrochloride: the teoclate salt acts longer than the hydrochloride and is used for motion sickness treatment and prevention, nausea, vomiting and labyrinthine disorders. The shorter-acting hydrochloride is used to treat both the symptoms and insomnia associated with urticaria and pruritus, allergy (hay fever and urticaria), emergency treatment of anaphylactic reactions, nausea, vomiting, vertigo, labyrinthine disorders and motion sickness.


Non-sedating antihistamines

Acrivastine provides symptomatic relief of allergy (e.g. hayfever) and chronic idiopathic urticaria. See PubChem CID 5284514 for chemical structure.

Cetirizine hydrochloride & its (R) enantiomer levocetirizine hydrochloride are are both licensed to provide symptomatic relief of allergy such as hay fever and urticaria. Cetirizine is further licensed for chronic idiopathic urticaria and atopic dermatitis. Chemically these are substituted analogues of cyclizine.

Loratadine & its (S) enantiomer desloratadine are licensed to provide symptomatic relief of allergy such as hay fever, chronic idiopathic urticaria. Desloratadine may be marginally superior in managing allergic rhinitis .


Other antihistamines    

Cyclizine is used extensively to treat nausea and vomiting associated with vestibular disorders and palliative care, vertigo and motion sickness. In addition to histamine receptor antagonist activity, cyclizine has significant central anticholinergic(antimuscarinic) activity which likely contributes to its anti-nausea effect.

Emedastine is found in opthalmic solutions used to provide relief from the symptoms of seasonal allergic conjunctivitis.

Epinastine hydrochloride is found in opthalmic solutions used to provide relief from the symptoms of seasonal allergic conjunctivitis.

Olopatadine hydrochloride is found eye drops used to relieve ocular inflammation associated with hay fever.