Antihistamine compounds

Reviews of recent developments in synthetic anti-spasmodics have been published by Raymond and by Blicke, and on the pharmacology of antihistamine compounds by Loew. Mention may also be made of the useful description by Henderson and Sweeten of the effeet of atropine on the gastro-intestinal canal and its glands. 

Antihistamine. Compound that, by occupying the histamine receptors, antagonizes the effects of histamine. 

Historically, both the tricyclic antipsychotic and antidepressant agents are derived in almost direct line from a series of tricyclic antihistaminic compounds (see 104 below). Minor changes in structure in some of the newer... 

A somewhat more complex theophylline derivative includes both the purinone nucleus and a piperazine side chain more commonly associated with HI antihistaminic compounds. The starting epoxide, 66, is available from treatment of the anion of purinone 65 with epichlorohydrin. Alkylation of the epoxide with monosubstituted piperazine derivative 67, leads to tazifylline (68) [11]. 

Bassano, J. L. Caille, E. J. (1979). Effects of two antihistaminic compounds (mequitazine, dexchlorpheniramine) on sleep. Sleep distortion by antihistaminics. Waking Sleeping 3, 57-61. 

Fig. 4.2 Penetration of antihistamine compounds into the CNS correlated with Diog P (log P cyclohexane - log P octanol) as a measure of hydrogen bonding potential.

Some of the more commonly used antihistamine compounds are listed below ... 

It is remarkable that, for histamine, very few compounds of plant origin have been found to have JI (or H2, H3, H4) -blocking properties (Fig. 18.17). a-Mangostin [28] is an example, although remarkably this compound (a competitive H, antagonist) does not carry a basic function. A basic tertiary amino group is also absent in cicletanide, an intriguing compound that has a chiral center and in which the antihistaminic activity resides in the levo isomer (Fig. 18.17). Rocastine and temelastine are two other antihistaminic compounds with unusual structures (Fig. 18.12). 

Casaban-Ros, E., Ant6n-Fos, G.M., Galvez, J., Duart, M.J. and Garcia-Domenech, R. (1999). Search for New Antihistaminic Compounds by Moleculm Connectivity. Quant.Struct.-Act.Relat., 18,35-A2. 

The antihistamine compound diphenhydramine is the major ingredient in nonprescription sleeping pills. 

Its actions on peripheral and cerebral vessels are thus similar to those of histamine and can L be antagonized by antihistaminic compounds 4. 

FIGURE 15.65 Variation of activity in a series of antihistaminic compounds as a function of the halogated para-substituentd ... 

A visible effect of the solubility modifications happening after introduction of a carboxylic group is found in the history of antihistaminic compounds (Figure 20.49). The first generation of antihistaminic drugs, in which hydroxyzine, were lipophilic compounds. They were able to cross the BBB, and had a sedating action because they were not P-glycoprotein (P-gp) substrate (which means they were not considered as xenobiotics and pumped out of the brain). Nowadays, hydroxyzine is still used as anxiolytic. 

The second generation of antihistaminic compounds are less lipophilic, thanks to the replacement of the hydroxy group by a carboxylic acid. They are also P-gp substrate, which limits CNS exposure. ... 

However, copper(II)(histamine)(Cl)2(HCl)2 has subsequently been found to be a potent antihistaminic compound having antiulcer and antisecretory activity [22, 267]. These and other data (p. 491) suggest that physiological levels of copper complexes have antihistaminic activity. 

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