The pharmacology of nedocromil sodium.
The pathophysiology of obstructive airways disease involves, in varying degree, components of reversible bronchoconstriction, inflammation and bronchial hyperreactivity. This multifactorial aetiology is the probable reason why no single animal model exists which is predictive of therapeutic efficacy in airway diseases, including asthma. Nedocromil sodium has therefore been profiled in a number of systems ranging from simple in vitro tests and in vivo models of passive anaphylaxis to complex models of anaphylactic bronchoconstriction in actively sensitized primates. Nedocromil sodium possesses efficacy and potency similar to those of sodium cromoglycate in classical passive models of immediate hypersensitivity in the rat. Preliminary studies have also shown that nedocromil sodium, like sodium cromoglycate, attenuates non-specific bronchial hyperreactivity in dogs exposed to sulphur dioxide. Extensive studies have been carried out in a model of airway disease in the primate Macaca arctoides infected with the nematode Ascaris suum. Bronchoalveolar cells obtained from these animals by lung lavage release substantial quantities of the inflammatory mediators histamine, leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) on immunological activation. Nedocromil sodium significantly inhibits the release of histamine, LTC4 and PGD2 from these cells in response to stimulation with antigen or antibody to human IgE. Under identical conditions, sodium cromoglycate has less than 1/200th the potency of nedocromil sodium, producing only insignificant inhibition of mediator release even at concentrations greater than 10(-4) M. A similar difference between the two drugs has been observed in vivo, where nedocromil sodium produced significant inhibition of antigen-induced bronchoconstriction in the Ascaris-sensitized macaque but sodium cromoglycate did not.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001985:Bronchial Provocation Tests; D004285:Dogs; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008251:Macaca; D008407:Mast Cells / Q000187:drug effects; D017835:Nedocromil; D010323:Passive Cutaneous Anaphylaxis; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D013189:SRS-A / Q000378:metabolism
D011457:Prostaglandins D; D011804:Quinolines; D013189:SRS-A; D017835:Nedocromil; D015230:Prostaglandin D2