(+)-Naloxone

(+)-Naloxone (dextro-naloxone) is a drug which is the "unnatural" enantiomer of the opioid antagonist drug (−)-naloxone. Unlike "normal" naloxone, (+)-naloxone has no significant affinity for opioid receptors, but instead has been discovered to act as a selective antagonist of Toll-like receptor 4. This receptor is involved in immune system responses, and activation of TLR4 induces glial activation and release of inflammatory mediators such as TNF-α and Interleukin-1.

Relation of TLR4 to opioid drugs

Both "normal" and "unnatural" enantiomers of various opioid analgesic drugs including morphine, meperidine, fentanyl, methadone and buprenorphine, as well as some otherwise inactive metabolites like morphine-3-glucuronide, have been found to act as agonists of TLR4, and chronic use of these drugs consequently causes constant low-level release of TNF-α and IL-1β as well as other downstream effects. This is thought to be involved in various adverse properties of opioid analgesic drugs, such as loss of efficacy with extended use and the associated development of tolerance and dependence, as well as the development of side effects such as hyperalgesia and allodynia, which can cause long-term use of opioid analgesics to not only fail to treat neuropathic pain, but ultimately exacerbate it.

Naloxone

Naloxone, sold under the brandname Narcan among others, is a medication used to reverse the effects of opioids, especially in overdose. Naloxone may be combined within the same pill as an opioid to decrease the risk of misuse. When given intravenously, it works within two minutes, and when injected into a muscle, it works within five minutes. The medication may also be used in the nose. The effects of naloxone last about half an hour to an hour. Multiple doses may be required, as the duration of action of most opioids is greater than that of naloxone.

Administration to opioid-dependent individuals may cause symptoms of opioid withdrawal, including restlessness, agitation, nausea, vomiting, a fast heart rate and sweating. To prevent this, small doses every few minutes can be given until the desired effect is reached. In those with previous heart disease, further heart problems have occurred. It appears to be safe in pregnancy, after having been given to a limited number of women. Naloxone is a pure opioid antagonist. It works by reversing the depression of the central nervous system and respiratory system caused by opioids.