GnRH analogoues-agonists and antagonists

Abstract

GnRH analogues have achieved widespread clinical use for control of reproduction in animals. Over 2000 analogues of GnRH have been developed and tested the last 30 years. Paradoxical anti-fertility effects are seen when the more potent agonists are delivered continuosly to animals. The evaluation of agonist potency depends largely on the model used and wide varying potencies are reported for same agonist. The design of analogues has centered on improving the receptors-binding and subsequent activation for agonists. Antagonists have been produced with strong receptor binding but without activation. Deslorelin is calssified as a superagonist,with a potency perhaps 100 times that of GnRH. the interactions between agonist potency,dose and duration of treatment largely determine whether pro- or anti-fertility effects are induced. Due to the peptide nature of the synthetic analogues, oral administration, and potential gastrointestinal enzymatic degradation, poor bioavailability results, necessitating a parenteral delivery system. Some GnRH antagonists have been associated with significant histamine release, inhibiting their widespread use. More recently,antagonists have been developed that avoid this side effect without compromising potency. However the GnRH antagonists development has lagged behind that of the agonists, in part related to their high cost of production. In conclusion ,GnRH agonists have achieved widespread clinical use in animals for controlling reproduction in either pro- or anti-fertility roles, antagonists development has been slower yet.