From morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller

Opium was known since the Neolithic era and in 5th century wild Papaver use was reported to induce sleep and relieving pain. First active component isolated from Opium was morphine, the paradigm of a natural product discovered 150 years before isolation of endogenous opioid ligands, brain pentapeptide enkephalins. Since then many endorphin peptides and their mode of action were discovered. Native endorphins were characterized thanks to the synthetic antagonist naloxone.