Abstract

Drugs which imitate endogenous agonist action are relatively rare and are restricted to those which replace systematically circulating hormones, are applied topically or are used for very short time periods. However, there is now much interest, especially in the biotechnology industry, in the development of agonist drugs. It is suggested that the successful clinical use of such drugs will be much more difficult than is usually anticipated. This is partly because, physiologically, most endogenous agonists are very restricted in their spatial distribution and it will not be easy to imitate such selected distribution patterns by exogenous administration. It is also partly because the effects of most agonists depend not only on the concentration present but also on the rate of change of concentration. Endogenous agonists often change their concentrations over seconds or less and again such temporal patterns will not easily be imitated by exogenous administration. Except when, as in the case with erythropoietin, the endogenous agonist circulates systemically and its levels fluctuate relatively slowly, the attempt to develop agonist drugs is likely to prove frustrating.