DEVELOPMENT OF ANALOGS - SUCCESSES AND FAILURES

The search for new pharmaceutical treatments has led to the isolation of products from a range of natural sources. Analogues synthesized fro m these products may possess an improved therapeutic effect over their natural counterparts. Two natural peptides, vasopressin and somatosta tin, possess pronounced in vivo effects, as do their analogues terlipr essin and octreotide. Vasopressin is a powerful vasopressor, reducing portal pressure, and has been used to treat gastrointestinal haemorrha ges. However, a number of adverse cardiovascular effects resulting fro m an increase in peripheral vascular resistance have been associated w ith this drug. Terlipressin, however, is more effective, has an improv ed safety profile and is associated with fewer side effects than vasop ressin. Somatostatin, a growth regulatory hormone, achieves haemostasi s by decreasing splanchnic blood flow, and is effective in preventing early rebleeding. Somatostatin is effective in treating bleeding oesop hageal varices (BOV) and is associated with fewer and more transient s ide effects than terlipressin. Octreotide, however, has greater stabil ity and a longer half-life than somatostatin, but has a less favourabl e safety profile. Octreotide displays a number of therapeutic advantag es over somatostatin, but not in the treatment of gastrointestinal ind ications. The development of terlipressin from vasopressin has demonst rated a number of clinical advantages, while the development of octreo tide from somatostatin has not shown any significant advantage in the treatment of BOV.