Development of preclinical models for testing antiasthma drugs

The antiasthmatic agent, sodium cromoglycate, owes its discovery to a series of antigen challenge tests carried out during the 1960s by an asthmatic, Roger Altounyan, on himself. Until recently, research efforts to identify new antiasthma drugs have relied heavily on screening methods which involved passively-sensitised mast cells. In theory these tests, such as rat passive cutaneous anaphylaxis, appeared relevant and showed sodium cromoglycate to have a stabilising effect on the mast cell membrane. In practice no new drugs were discovered, since this type of activity in animal models was not predictive of antiasthmatic potential. A more relevant research programme has subsequently evolved, which attempts to approach more closely the conditions prevailing in the asthmatic lung. The use of a model of immune lung inflammation in macaque monkeys in conjunction with a model of bronchial hyper-reactivity in the dog has been successful in producing the new compound, nedocromil sodium, which is proving to be an effective addition to the drugs available for the treatment of inflammatory diseases of the airways.