Antihistamines, specific agents

Further illustration for the lack of structural specificity required for antihistaminic activity comes from the finding that ethylenediamines carrying both a benzylamine and an additional aromatic substituent on one of the nitrogens afford a series of useful therapeutic agents. Alkylation of benzylaniline with JV-... 

The low order of structural specificity required for classical antihistaminic activity was noted earlier. It has been found possible to substitute an indene nucleus for one of the two aromatic rings that most of these agents possess. The basic side chain may be present as either dimethylaminoethyl or itself cyc-lized to provide an additional fused ring. 

Hf and H Receptors. Histamine exerts its actions by binding to receptors on cell membranes. Two types of histamine receptors, the Hi and H2 receptors, are known specific agonists and antagonists exist for each of these receptors. Black et al. (55) differentiated H and H2 receptors with the compounds, 2-methylhistamine and 4 methylhistamine. 2-Methylhistamine is active on tissues with H receptors 4-methylhistamine is active on tissues with H2 receptors. Classical antihistaminic drugs were developed in the 1930 s these compounds block H but not H2 receptors. Among the clinically used H -blockers are derivatives of ethanolamine, ethylenediamine, alkylamine, piperazine and phenothiazine (32). These agents are valuable in the treatment of... 

Some ADRs are caused by most or all medications in a class, while others are agent specific. Nausea, vomiting, and diarrhea have been observed with most antibiotics, yet only chloramphenicol and certain sulfonamide antibiotics have been consistently implicated as causes of aplastic anemia. Some pharmacological effects, such as sedation from an antihistamine, may be considered adverse effects when they are... 

Anti-inflammatory compounds can act at different levels. They can, for example, decrease vasodilatation and edema, as in the case of antihistaminic drugs inhibit PGs synthesis as do the non-steroidal antiinflammatory drugs modify synthesis or block the receptors of mediators such as PAF or LTs interfere with the functions of peptide mediators block the transcription factors or scavenge free radicals generated in the process. Natural products as anti-inflammatory agents may act at different levels, some by non specific pathways as antioxidants do or by a specific mechanism via receptor antagonism. The lignans can act in both cases. 

The antihistamine hydroxyzine is an effective antianxiety agent, but only at doses (-400 mg/day) that produce marked sedation (see Chapter 24). Propranolol and metoprolol, lipophilic fi adrenergic receptor antagonists that enter the CNS, can reduce the autonomic symptoms (nervousness and muscle tremor) associated with specific situational or social phobias but do not appear to be effective in generalized anxiety or panic disorder (see Chapter 10). Similarly, other antiadrener-gic agents, including clonidine, may modify autonomic expression of anxiety but are not demonstrably usfful in the treatment of severe anxiety disorders. 

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