Renin Inhibitor - History

History

In 1896, the Finnish physiologist Robert Tigerstedt and the Swedish physician Per Bergman did an experiment on kidneys and the circulatory system in rabbits. They observed that blood pressure rose in the rabbits when extracts of the kidneys were injected into their jugular veins. They also discovered this substance responsible for higher blood pressure was produced in the renal cortex, and they named it renin. Although this experiment laid the foundation for future investigations into the RAAS pathway, it had little impact on the scientific community at that time. In 1934, when Goldblatt published his work in renal ischaemia, renin came into focus again. The importance of renin in the pathogenesis of cardiovascular disease was, however, not fully understood until in the 1970s, and 20 years later the first renin inhibitors went to clinical trials.

Pepstatin, which was described in 1972, was the first synthetic renin inhibitor, but poor pharmacokinetic properties prevented it from entering in vivo investigations. The first generation of renin inhibitors, such as H-142, were peptide analogues of angiotensinogen. However, these inhibitors had also limited drug-like properties. Hopes of breakthrough appeared in 1982 when development of the second generation renin inhibitors began. This generation consisted of peptide-like compounds, such as remikiren, enalkiren and zanikiren. They had more drug-like rather than substrate-like properties, and in 1990 they went to clinical trials. The second generation had its limitations and never completed clinical trials.

Aliskiren, the only renin inhibitor to go into phase III clinical trials, is not structurally related to peptides, which makes it a third-generation renin inhibitor. The first clinical trial was performed in 2000 in healthy volunteers. In 2007, aliskiren was approved by the US Food and Drug Administration and the European Medicines Agency as a treatment for hypertension.

Read more about this topic:  Renin Inhibitor

Famous quotes containing the word history:

    What is most interesting and valuable in it, however, is not the materials for the history of Pontiac, or Braddock, or the Northwest, which it furnishes; not the annals of the country, but the natural facts, or perennials, which are ever without date. When out of history the truth shall be extracted, it will have shed its dates like withered leaves.
    Henry David Thoreau (1817–1862)

    In every election in American history both parties have their clichés. The party that has the clichés that ring true wins.
    Newt Gingrich (b. 1943)

    I assure you that in our next class we will concern ourselves solely with the history of Egypt, and not with the more lurid and non-curricular subject of living mummies.
    Griffin Jay, and Reginald LeBorg. Prof. Norman (Frank Reicher)