Eltanolone: 50 years on and still looking for steroid hypnotic agents!

The knowledge that steroids can induce and maintain sition as the sodium hemisuccinate. Hydroxydione had a high therapeutic index, and few adverse effects anaesthesia is not new; in 1927, Cashin and Moravek caused hypnosis in cats by using a colloidal susin cats and dogs [4]. In clinical practice, hydroxydione produced minimal pension of cholesterol [1]. However, present-day interest in these molecules stems from the systematic changes in cardiorespiratory function, good muscle relaxation, a low incidence of coughing and pleasant review of the hypnotic properties of steroids (mainly belonging to the pregnane and androstane groups) recovery, with a very low incidence of vomiting [5,6]. However, induction took several minutes. As there by Selye in 1941 [2]. There was no apparent relation between hypnotic (anaesthetic) and hormonal propwas early obtunding of the pharyngeal and laryngeal reflexes, it was possible to achieve airway intubation. erties in any of the screened steroids; the most potent anaesthetic steroid, pregnane-3,20-dione The respiratory rate increased with an accompanying decrease in tidal volume and with a resulting increase (pregnanedione), was virtually devoid of endocrinological activity. in minute volume. Marked respiratory depression and apnoea were not usually seen. Cardiac output and However, one of the major problems with these steroidal agents was their poor water solubility, and arterial blood pressure also fell. However, there were several unwanted side effects: pain on injection; and little further work was conducted until Laubach and colleagues synthesized hydroxydione [3]. This was the a high incidence of post-anaesthetic irritation at the site of intravenous (i.v.) administration and along the 21-hydroxy derivative of pregnanedione, which was made water soluble by esterification at the C21 poassociated vein.