Oxytocin, Carbetocin

Category: Peptide hormones and their analogues

Registration & producers: Oxytocin 1958 (Léčiva, Ferring); Carbetocin: Depotocin 1992 (NORDIC Pharma) – veterinary, Duratocin 2006 (Léčiva, Ferring, PolyPeptide Laboratories) – human 

Oxytocin is a human neurohypophyseal hormone, which today is produced on a large scale using synthetic methods. It is currently used as an essential drug in gynecology and obstetrics for labor facilitation.

Oxytocin was first artificially synthesized by Vincent du Vigneaud, who in 1955 received the Nobel Prize for his research on the hormone. At IOCB, Josef Rudinger and his team developed the first feasible method for industrial production of oxytocin, which was begun in Prague in 1958 by the pharmaceutical company Léčiva. Further studies on amino acid residue replacement in various positions resulted in the preparation of multiple hormone analogues. The first useful oxytocin analogue (Tyr(OMe)2-oxytocin, also known as methyloxytocin), was developed in 1966 and is used in protracted deliveries.

Carbetocin is an oxytocin analogue with a so-called carba modification of the disulfide bridge. This modification, developed by Karel Jošt and Josef Rudinger in 1964, makes carbetocin metabolically stable and is responsible for its long-lasting effect. Analogues with the carba modification were later extensively studied at IOCB.

Carbetocin is used in obstetrician medicine to treat protracted labor and stop bleeding and hemorrhage following cesarean section. Despite its promising biological activity and enhanced metabolic stability, for many years it was used in veterinary medicine only. Recently, it has been approved for human use in many countries. A carbetocin analogue with selective natriuretic activity, [2-p-ethylphenylalanine] deamino-6-carba-oxytocin (nacartocin), which was developed by Lebl and Jošt in 1984, was recently tested in a clinical trial.

Research in neurohypophyseal hormones ceased following the untimely death of Karel Jošt in 1986 and the departure of peptide department head Michal Lebl in 1991.