Iron is essential for all human cells as well as neoplastic cells and invading microbes. Natural and synthetic iron chelators could affect biological processes involving iron and other metal ions in health and disease states. Iron overload is the most common metal toxicity condition worldwide. There are currently two iron chelating drugs, which are mostly used for the treatment of thalassaemia and other conditions of transfusional iron overload. Deferoxamine was until recently the only approved iron chelating drug, which is effective but very expensive and administered parenterally resulting in low compliance. Deferiprone (L1 or 1,2-dimethyl-3-hydroxypyrid-4-one) is the world's first and only orally active iron chelating drug, which is effective and inexpensive to synthesise thus increasing the prospects of making it available to most thalassaemia patients in third world countries who are not currently receiving any form of chelation therapy. Deferiprone has equivalent iron removal efficacy and comparable toxicity to deferoxamine. There are at least four other known iron chelators, which are currently being developed. Even if successful, these are not expected to become available for clinical use in the next five years and to be as inexpensive as deferiprone. The variation in the chemical, biological, pharmacological, toxicological and other properties of the chelating drugs and experimental chelators provide evidence of the difference in the mode of action of chelators and the need to identify and select molecular structures and substituents based on structure/activity correlations for specific pharmacological activity. Such information may increase the prospects of designing new chelating drugs, which could be targeted and act on different tissues, organs, proteins and iron pools that play important role not only in the treatment of iron overload but also in other diseases of iron and other metal imbalace and toxicity including free radical damage. Chelating drugs could also be designed, which could modify the enzymatic activity of iron and other metal containing enzymes, some of which play a key role in many diseases such as cancer, inflammation and atherosclerosis. Other applications of iron chelating drugs could involve the detoxification of toxic metals with similar metabolic pathways to iron such as Al, Cu, Ga, In, U and Pu.

Whole blood 5HT levels were measured in seven female migraine sufferers with chronic daily headache due to medication abuse, before and after abrupt medication withdrawal. A statistically significant increase in 5HT levels, from mean 4.89 mumol/l to mean 6.59 mumol/l (p < 0.05, Wilcoxon signed rank test), occurred after 4 weeks of withdrawal. We conclude from this pilot study that 5HT may be important in the physiopathogenesis of chronic daily headache. Alternatively, reduced 5HT may be the result of chronic daily headache or else an epiphenomenon.

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Histamine, a biogenic amine, is involved in allergic reactions and asthma. The involvement of histamine in peptide ulcers is reviewed here. The discovery, distribution, synthesis, catabolism, and pharmacological effects of histamine are briefly described. Histamine actions are mediated by more than one type of receptor. The discovery, development and mode of action of H2-antagonists is discussed. A brief comparison of the clinical profiles (dosage regimen, metabolism and drug interactions) of the four currently used H2-antagonists (cimetidine, ranitidine, nizatidine and famotidine) is given. Furthermore, due to their ability to bind to cytochrome P-450, these compounds have the potential to interfere with the hepatic clearance of other drugs which are also metabolised by the mixed-function oxidase system in man. Therefore, a brief discussion of their adverse effects and drug interactions is included. Modulation of gastric acid secretion, in particular the role of cAMP and the proton pump, is described. Peptic ulcer is a major disease in the Western world and the aetiology and treatment of peptic ulcer are summarised.