Antihistaminics

Histamine is responsible for many of the symptoms associated with hay fever and other allergies An antihistamine relieves these symptoms by blocking the action of histamine... 

Miscellaneous Pharmaceutical Processes. Solvent extraction is used for the preparation of many products that ate either isolated from naturally occurring materials or purified during synthesis. Among these are sulfa dmgs, methaqualone [72-44-6] phenobarbital [50-06-6] antihistamines, cortisone [53-06-5] estrogens and other hormones (qv), and reserpine [50-55-5] and alkaloids (qv). Common solvents for these appHcations are chloroform, isoamyl alcohol, diethyl ether, and methylene chloride. Distribution coefficient data for dmg species are important for the design of solvent extraction procedures. These can be determined with a laboratory continuous extraction system (AKUEVE) (244). 

This compound has antihistaminic activity and is usehil in the therapy of motion sickness. It may also be effective in the control of post-operative nausea and vomiting. It is classified as FDA Category B for Pregnancy, ie, no demonstrated risks shown in animal studies however, no controlled trials in pregnant women. Large doses may cause drowsiness and dry mouth owing to decreased secretion of saUva. 

The history of histamine [51-45-6] (1), and the development of antihistamines have been reviewed (1,2). Histamine was the first to be... 

In 1966, the name was proposed (5) for receptors blocked by the at that time known antihistamines. It was also speculated that the other actions of histamine were likely to be mediated by other histamine receptors. The existence of the H2 receptor was accepted in 1972 (6) and the receptor was recognized in rat brain in 1983 (7). receptors in the brain appear to be involved in the feedback control of both histamine synthesis and release, whereas release of various other neurotransmitters, eg, serotinin (5-HT), dopamine, noradrenaline, and acetylcholine, is also modulated (8) (see Neuroregulators). 

Hj Antihistamine Treatment in Allergic Diseases. H -receptor antagonists are used for the symptomatic treatment of several allergic... 

Clinically Efficacy. It is evident from the mechanism of action of antihistamines and the etiology of allergic diseases that antihistamines in no sense achieve a cure of the patient s allergy. After the adrninistration of a therapeutic dose, a temporal blockade of the effects of histamine is obtained. Whereas classical antihistamines needed at least twice daily adrninistration, for most of the more recently introduced agents adrninistration once daily is sufficient. 

Nevertheless, although the nonsedating H antihistamines have substantially improved the acceptabiUty and clinical efficacy of this class of compounds, these do not provide complete rehef eye disease responds less well than nasal disease, of the rhinitis symptoms nasal congestion responds poorly, breakthrough symptoms occur at high poUen counts, and only some 70% of patients report excellent to good treatment responses. Considerable research therefore still continues in the H antihistamine field. New antihistamines are continually being introduced. 

Topical Application. Azelastine (11) and levocabastine (13) have been developed for topical appHcation (45). The topical antihistamines address the preference of some patients for a local treatment and allow adrninistration of dmg directly to the site requited. The advantage of this therapeutic approach is likely to be in the speed of onset of symptom rehef. In contrast to earlier reports of sensitization with older antihistamines locally apphed to the skin (46), sensitization has not been reported with local appHcation to the nose or eyes. 

Lithium Amide. Lithium amide [7782-89-0], LiNH2, is produced from the reaction of anhydrous ammonia and lithium hydride. The compound can also be prepared by the removal of ammonia from solutions of lithium metal in the presence of catalysts (54). Lithium amide starts to decompose at 320°C and melts at 375°C. Decomposition of the amide above 400°C results first in lithium imide, Li2NH, and eventually in lithium nitride, Li N. Lithium amide is used in the production of antioxidants (qv) and antihistamines (see HiSTAMlNE AND HISTAMINE ANTAGONISTS). 

Another large-volume use for organ olithium compounds is in the synthesis of pharmaceutical and agricultural chemicals, eg, antibiotics (qv), antihistamines, antidepressants, anticoagulants, vasodilators, tranquiU2ers, analgesics, fungicides, and pesticides (116—119). 

The principal OTC pharmaceutical products include cold remedies, vitamins and mineral preparations, antacids, analgesics, topical antibiotics, antiftingals and antiseptics, and laxatives. Others include suntan products, ophthalmic solutions, hemorrhoidal products, sleep aids, and dermatological products for treatment of acne, dandmff, insect parasites, bums, dry skin, warts, and foot care products (11). More recent prescription-to-OTC switches have included hydrocortisone, antihistamine and decongestant products, antiftingal agents, and, as of 1995, several histamine H2-receptor antagonists. 

Two newer potent selective H -antagonists, terfenadine (23) (132) and astemizole (24) (133), have been developed which have neither the sedative nor the anticholinergic Habilities of the earlier agents. Both of these compounds have proven efficacious in the treatment of hay fever and produce very few side effects, prompting a re-evaluation of the role of antihistamines in asthma treatment. 

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