

Based on the dictum: No acid – no ulcer a number of pharmaceutical companies started up research aiming at a drug, inhibiting gastric acid secretion during 1960s. The focus of that research was gastrin, the gastric acid stimulating hormone released from G-cells in the antral part of the stomach. The Searle company in the US tried to find a small molecule inhibiting the gastrin receptor, while AstraHässle in Sweden tried to find something that decreased the release of gastrin from the G-cells. SK&F focused on the H2-receptor also involved in the regulation of gastric acid secretion. The SK&F approach lead to the first clinically useful acid inhibitor, cimetidine. The AstraHässle approach was a dead end, as was the Searle approach. However, the Searle idea led to the discovery of CMN 131, a compound which had some acid inhibitory effect, but was also toxic. When AstraHässle failed with their first attemptthey picked up on CMN 131 as a new lead around 1972. This approach resulted in timoprazole (1974), picoprazole (1977), and eventually omeprazole (1979). Omeprazole was first launched in Sweden 1988, under the trade name Losec. In 1997 Losec reached a yearly sale of more that 6 billion USD and became the world's biggest drug.
The AstraHässle project, which ended up with the approval of omeprazole 1988, started already 1967. Thus it took more than 20 years from the idea to market. Would that have been possible today with the present time-press and recourse restrictions within drug industry? It's doubtful. The struggle and issues to be solved during the journey are described.