The neuroactive steroid anaesthetics are the safest agents on record with therapeutic indices (lethal dose/anaesthetic dose) of 20-30 or more compared with 4-6 for the barbiturates and propofol and 8-10 for midazolam and ketamine.
Alfaxalone is a neurosteroidal general anaesthetic which is currently used widely in veterinary applications. It is a preferred anaesthetic for short duration operations due to its rapid half life and clearance. In addition it has a large therapeutic window making it very safe. However it is not currently used as widely as clinicians would like, due to significant levels of neuromotor excitation resulting in muscle twitching/limb movement/vocalization during anaesthesia or recovery from anaesthesia. This has also contributed to it not being pursued for human use. Alfaxalone has a number of properties which make it extremely desirable in both the animal and human anaesthesia markets if this issue was to be addressed.
Researchers within the School of Biomedical Sciences have identified that the cause of the neurostimulation is through the suppression of an inhibition pathway within the motor neurons. It was found that neurotransmitters released through specific receptors were unregulated in these subjects. More recently through the use of tool compounds it has been shown in vitro and in vivo that through antagonizing these receptors neuroexcitation can be eliminated.