New glucocorticosteroids with an improved therapeutic ratio?

Glucocorticoids (GCs) remain the most effective therapy for inflammatory disorders. In terms of asthma, topical steroids are the mainstay for controlling the inflammatory component of the disease. However, their use is limited by the constellation of adverse effects associated with chronic, oral steroid use and the longterm adverse effects associated with inhaled steroid use. These include suppression of hypothalamic-pituitary axis, osteoporosis, reduced bone growth in the young, opportunistic infections, behavioural alterations, and disorders of lipid metabolism, Most of these effects may be attributable to the endocrine activity of steroids and are largely identical to the syndromes of endogenous corticosteroid excess (Cushing's Syndrome). Thus, the Holy Grail of steroid pharmacology is the development of agents which have a markedly improved therapeutic ratio than current steroids, especially on systemic administration. This may be achieved by the identification of molecules which elicit marked antiinflammatory effects, but have a minor impact on endocrine responses. Dissociated corticosteroids are ligands for the glucocorticoid receptor that may offer the potential for a more selective antiinflammatory profile, (C) 2001 Academic Press.