New research on the rare amino acid isovaline shows that it could act as an effective pain reliever with few side effects. Injecting mice with the amino acid inhibits the nervous system’s processing of pain, acting as both an ant nociceptive and an antiallodynic drug. In combination with propofol, isovaline could make procedural sedation significantly more effective and safe.
With potential applications such as these, one might wonder why isovaline’s properties have only recently been revealed. One reason is the amino acid’s unusual origin. Isovaline is extraterrestrial: it first appeared on Earth in 1969 when the Murchison meteorite crashed into Australia. The meteorite also contained common amino acids such as glycine and alanine.
Isovaline works as an analgesic because of its structural similarity to two neurotransmitters responsible for inhibiting pain in the central nervous system: glycine and GABA. These agonists reduce how much pain a person feels by fitting themselves into specially-shaped receptors. Chronic pain arises when there are not enough of these inhibitory agonists, and too many pain signals coming from free nerve endings or other sources. Isovaline can counteract this imbalance by acting as a substitute for glycine and GABA. By activating pain-inhibiting receptors, isovaline is an artificial substitute for the neurotransmitters.
In addition to its effectiveness as an analgesic, isovaline possesses the additional benefit of having no major side effects. Many drugs that relieve pain also cause confusion, sedation, respiratory depression, or addiction. Isovaline is a small molecule that does not cross the blood-brain barrier, and as such produces analgesia without a noticeable effect on the central nervous system. Mice injected with the amino acid both by IV and into the spinal theca experienced no alteration in their spontaneous activity, gait, posture, or respiratory rate.
A study just published in December of 2015 demonstrates isovaline’s potentially significant contribution to medicine as an adjuvant for propofol, the hypnotic agent that is increasingly used in procedural sedation. There is a pressing need to make propofol safer for patients. Sometimes the people who administer propofol are not trained in airway management. Lately the news has published stories about propofol-related respiratory complications, some of which have ended in death.
A mixture of propofol, which on its own causes hypnosis, and an analgesic like an opioid can result in general anesthesia. Under the power of these combined agents a patient both forgets what happened during the procedure and does not experience pain. The combination of opioid and propofol is effective but can lead to respiratory depression relatively easily.
This is where isovaline comes in. As a non-sedating analgesic, isovaline potentially provides the pain-relief of an opioid without the danger of respiratory complications. The recent study shows that isovaline combined with propofol can yield effective general anesthesia: hypnosis, analgesia, and conscious sedation.
If isovaline turned out to be a viable drug for human use, many patients may benefit. Patients would recover from general anesthesia more quickly and experience fewer adverse effects, reducing their health care costs. Medical centers would benefit from the increase in patient and staff satisfaction. And most importantly, the number of sedation-related deaths and complications could potentially be diminished.