Introduction

The appearance of non-sedating antihistamines has provided the opportunity to reassess the role of histamine in various allergic diseases. Firstly, these antihistamines selectively block histamine receptors, although they indirectly influence the following mediator-cascade. Secondly, peripheral histamine receptors can be blocked to a much higher extent because the administration of these drugs up to high peripheral histamine blockade levels is not prevented by central nervous system (CNS) side-effects. Thirdly, because these substances show only few or no sedating side-effects, sedation is less likely to influence the results obtained in clinical studies. Non-sedating antihistamines have been available in most countries for several years now. Their clinical benefit has been proven in classical indications such as hay fever and acute urticaria. They have also been studied in disease areas less traditionally associated with antihistamine therapy, such as asthma, atopie dermatitis, chronic forms of urticaria, etc. Has this been a successful exercise? This intriguing question was posed at the session Antihistamines Reassessed; Past, Present and Future, held at the XlVth Congress of the European Academy of Allergology and Clinical Immunology in Berlin. The papers presented at this session have been collected in this supplement. Antihistamines have come a long way, from the first non-specific and sedating antihistamines to the currently available, highly specific and selective antihistamines. Nevertheless, characteristics other than Hpblockade have been described for these new substances as well. 'How specific are the non-sedating antihistamines?' and 'what is the relevance of other characteristics?', are subjects dealt with by Janet Rimmer and Martin Church. Great care seems warranted in interpreting the clinical relevance of pharmacological findings observed at concentrations exceeding by far the therapeutic levels. The non-sedating Hi-receptor antagonists differ considerably in their human pharmacokinetic characteristics. Such pharmacokinetic data provide essential elements for the interpretation of clinical pharmacology results, although a close correlation is not an absolute rule, as discussed by Estelle Simons. In the upper airways, histamine is still the major mediator which is consistently released after appropriate challenge, and produces the major symptoms of rhinitis. The new specific antihistamines have confirmed their role by reducing the symptoms both in challenge situations and during natural allergen exposure. As documented by Ulf Pipkorn, approaches other than H|-antagonism should be looked for if we want an optimal control of blocked nose and of the inflammatory response. The advent of the non-sedating antihistamines has enabled a reappraisal of the role of histamine in asthma. It is clear that the caution about the use ofthe early non-specific antihistamines in asthma does not apply to the non-sedating substances. With the present experience, Peter Howarth's conclusion that Hi-receptor stimulation is not THE major pathological factor seems justified. H|-antihistamines can be supportive but not a prime therapy in asthma in adults. The role of histamine in skin allergies has definitely been confirmed. Its action is not limited to a stimulation ofthe Hi-receptors. As Johannes Ring and Hans Behrendt state, H2-receptor stimulation is likely to be of clinical relevance as well. Further research on the use of a combined H1-H2 blockade in pseudoallergic conditions is indicated. I join Alain De Week in his eonclusion that the appearance of new, more potent Hi-antagonists, with no or fewer side-effects, has led to a reassessment of their use. The new substances have consolidated the first line role of antihistamines in allergic rhinitis and skin allergies. They have a more favourable position in asthma than their less selective predecessors. With Hpstimulation being easily controllable nowadays, further progress in treating the allergic patient should be sought in new approaches rather than in minor variations to existing themes. The support of Janssen Pharmaceutica in publishing this review supplement on the present knowledge of histamine and its modern antagonists is greatly appreciated.