Agents antihistaminic

Fischer indole condensation of Ni-benzylphenyl-hydrazine and 1-methyl-4-piperidone under the usual acid conditions affords meb-hydroline (29), an indole used as an antihistaminic agent-... 

Benzimidazoles are generally synthesized from ortho-diamino-benzenes and carboxylic acid derivatives. The antihistaminic agent, clemizole (60), for example, can be prepared by first reacting ortho-diaminobenzene (57) with chloroacetic acid to form 2-chloro-methylbenzimidazole (58). Displacement of the halogen with pyro-... 

Demethylation of the tricyclic antihistamine 9, with cyanogen bromide gives the secondary amine 10 acylation of that intermediate with ethyl chloroformate affords the nonsedating H-1 antihistaminic agent loratidine (11) [3], It is of interest that this compound does not contain the zwitterionic funcrion which is thought to prevent passage through the blood-brain barrier, characteristic of this class of compounds. 

A slightly more complex Scheme is required for preparation of an antihistaminic agent bearing a secondary amine, e. g., tofenacin (32). In the synthesis of tofenacin, alkylation of the benzhydrol (29) with ethyl bromoacetate affords the alkoxy ester (30) saponification followed by conversion to the methylamide gives (31), which is reduced with lithium aluminum hydride to complete the synthesis of 32. 10... 

Dixon and Mountain reported that exposure of mice to ozone at 1 ppm for 5 h resulted in a depletion of lung histamine content to as low as 75% of the control value 5 days later. They also observed that pretreatment with promethazine, an antihistaminic agent, resulted in a decrease in the amount of pulmonary edema produced by a sublethal dose of ozone. However, promethazine, in addition to being a potent antihistaminic agent, is a phenothiazine derivative and thus might act to trap fiee radicals or stabilize membranes. 

Another important use of Hj-antagonists is in the treatment of motion sickness. Diphenhydramine (Benadryl), dimenhydrinate (Dramamine), cyclizine (Marezine), and meclizine (Antivert) have anticholinergic activity and are the preferred antihistaminic agents for reducing the symptoms of motion sickness. 

Other important pyrimidinone derivatives include temelastine 1123, an antihistaminic agent, urapidil 1124, an antihypertensive, and 5-hydroxymethyl-6-methyluracil (pentoxyl) 1125 which is used as a leukopoietic stimulant in wound healing. 

It is antihistaminic agent having antiemetic, sedative, anticholinergic and local anaesthetic property. Used in anxiety, pruritus and dermatoses as an adjunct therapy in acute/ chronic alcoholism. 

The newer antihistaminics agents e.g. Azelastme inhibits histamine release and also inflammatory reactions evoked by leukotrienes and plasma activating factor (PAF). It is used for seasonal and perennial allergic rhinitis in the form of nasal spray. Mizolastine, a non-sedating antihistaminic is used in allergic rhinitis and urticaria. Ebastine, another non-sedating antihistaminic is used in nasal and skin allergies. 

Doxylamine succinate etc. Details are given in chapter Antihistaminic agents . 

For the synthesis of cetirizine hydrochloride 45, diarylmethylamine 47b was of particular importance, since deprotection under acidic conditions led to 49, which is a known intermediate for the synthesis of the desired antihistamine agent. As... 

Enantiomerically pure diarylmethylamines are important intermediates in the synthesis of biologically active compounds such as 28 or 29 (Fig. 2.1.3.8). Among several drug candidates, Cetirizine hydrochloride (28) stands out as a commercially important nonsedative antihistamine agent. Binding studies indicate that... 

Benzimidazoles substituted with an alkylamine at position 2 have a venerable history as Hi antihistaminic agents. The standard starting material for many benzimidazoles consists of phenylenediamine (40-1), or its derivatives. Reaction of that compound with chloroacetic acid can be rationalized by invoking initial formation of the chloromethyl amide (40-2). Imide formation with the remaining free amino group closes the ring to afford the 2-chloromethyl benzimidazole (40-3). Displacement of... 

Certain vestibular disorders respond to antimuscarinic drugs (and to antihistaminic agents with antimuscarinic effects). Scopolamine is one of the oldest remedies for seasickness and is as effective as any more recently introduced agent. It can be given by injection or by mouth or as a transdermal patch. The patch formulation produces significant blood levels over 48-72 hours. Useful doses by any route usually cause significant sedation and dry mouth. 

Angioedema may be precipitated by histamine release but appears to be maintained by peptide kinins that are not affected by antihistaminic agents. For atopic dermatitis, antihistaminic drugs such as diphenhydramine are used mostly for their sedative side effect, which reduces awareness of itching. 

It has been claimed that the antihistaminic agents effective in prophylaxis of motion sickness are also useful in Meniere s syndrome, but efficacy in the latter application is not established. 

Cyproheptadine resembles the phenothiazine antihistaminic agents in chemical structure and has potent H receptor-blocking as well as 5-HT2-blocking actions. The actions of cyproheptadine are predictable from its histamine and 5-HT receptor affinities. It prevents the smooth muscle effects of both amines but has no effect on the gastric secretion stimulated by histamine. It also has significant antimuscarinic effects and causes sedation. 

Iodinated glycerol, another agent that is often combined with dextromethorphan, functions as an expectorant. Promethazine hydrochloride is an antihistamine agent sometimes combined with dextromethorphan. 

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