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In 1941, Hans Selye discovered that some steroid compounds produced anaesthesia. The following year he conducted experiments with 75 steroids which were dissolved in peanut oil and given intraperitoneally to partially hepatectomized rats. He stated, "the most striking fact which emerges from a perusal of the data is that all preparations that are known to possess hormonal properties are active as anaesthetics". Of all the preparations that he studied, pregnandione was the one that showed a particularly marked narcotic effect. Unfortunately pregnandione is almost insoluble in water which made intravenous administration difficult. Further research was performed using subcutaneous pregnandione in peanut oil on young rats, Anaesthesia was produced relatively quickly but the rats slept for 26 hours!
This research led Laubach, P'an and Rudel to experiment with 21-hydroxypregnanedione sodium hemisuccinate (hydroxydione), a water soluble derivative of pregnandione. This compound was manufactured by the Pfizer company as Viadril and clinical trials were commenced in 1955 by F. J. Murphy and colleagues on 125 patients. They found it to be a satisfactory anaesthetic agent when used with nitrous oxide and oxygen, with or without opioids and muscle relaxants.
The following year further clinical trials were reported by R. A. Gordon and colleagues from Toronto General Hospital. "The drug is supplied as a white powder which is readily soluble in water. Since it is a soap, it tends to foam, and this characteristic can be a nuisance in the preparation of solutions. It is irritating to tissues and tends to produce thrombosis of the veins." They experimented with various dose and dilution regimens...