Naloxone and naltrexone are commonly used opioid antagonist drugs which are competitive antagonists that bind to the opioid receptors with higher affinity than agonists but do not activate the receptors. This effectively blocks the receptor, preventing the body from responding to opiates and endorphins.
Some opioid antagonists are not pure antagonists but in fact do produce some weak opioid partial agonist effects, and can produce analgesic effects when administered in high doses to opioid-naive individuals. Examples of such compounds include nalorphine and levallorphan. However the analgesic effects from these drugs are limited and tend to be accompanied by dysphoria, most likely due to action at the kappa opioid receptor. As they induce opioid withdrawal effects in people who are taking, or have recently used, opioid full agonists, these drugs are considered to be antagonists for practical purposes.
The weak partial agonist effect can be useful for some purposes, and has previously been used for purposes such as long-term maintenance of former opioid addicts using nalorphine, however it can also have disadvantages such as worsening respiratory depression in patients who have overdosed on non-opioid sedatives such as alcohol or barbiturates. Naloxone on the other hand has no partial agonist effects, and is in fact a partial inverse agonist at mu opioid receptors, and so is the preferred antidote drug for treating opioid overdose.
Naltrexone is also a partial inverse agonist, and this property is exploited in treatment of opioid addiction, as a sustained course of low-dose naltrexone can reverse the altered homeostasis which results from long-term abuse of opioid agonist drugs. This is the only treatment available which can reverse the long-term after effects of opioid addiction known as post acute withdrawal syndrome, which otherwise tends to produce symptoms such as depression and anxiety that may lead to eventual relapse. A course of low-dose naltrexone is thus often used as the final step in the treatment of opioid addiction after the patient has been weaned off the substitute agonist such as methadone or buprenorphine, in order to restore homeostasis and minimise the risk of post acute withdrawal syndrome once the maintenance agonist has been withdrawn.
All of the opioid antagonists used in medicine are non-selective, either blocking all three opioid receptors, or blocking the mu-opioid receptor but activating the kappa receptor. However for scientific research selective antagonists are needed which can block one of the opioid receptors but without affecting the other two. This has led to the development of antagonists which are highly selective to one of the three receptors;
- Cyprodime is a selective mu opioid receptor antagonist
- Naltrindole is a selective delta opioid receptor antagonist
- Norbinaltorphimine is a selective kappa opioid receptor antagonist
Other selective antagonists are also known, but the three listed above were the first selective antagonists discovered for each respective opioid receptor, and are still the most widely used.
Naloxone and naltrexone have both been studied for the treatment of depersonalization disorder. In a 2001 study with naloxone, three of fourteen patients lost their depersonalization symptoms entirely, and seven showed marked improvement. The findings of a 2005 naltrexone study were slightly less promising, with an average of a 30% reduction of symptoms, as measured by 3 validated dissociation scales. The more dramatic result of naloxone versus naltrexone is suspected to be due to different endogenous opioid receptor selectivity in naloxone, which is better suited to individuals suffering from depersonalization disorder.
- In the episode of House, "Skin Deep", opioid antagonist drugs were administered in order to completely remove the patient's heroin induced addiction/withdrawal symptoms (during an induced coma in order to relieve the extreme pain of their use), so that an accurate diagnosis of paraneoplastic syndrome caused by cancer was differentiated.
- In an episode of Royal Pains, a character dangerously tries to undergo a procedure (and go under anaesthesia) in his own home.
- In an episode of Hannibal, Lecter administers Naloxone to Jack Crawford's wife after she tries to commit suicide by overdosing on her morphine.
- David S, Lancaster T, Stead LF. Opioid antagonists for smoking cessation (Cochrane Review), The Cochrane Library, Issue 2, 2005. Chichester, UK: John Wiley & Sons, Ltd.
- Opioid Antagonists at the US National Library of Medicine Medical Subject Headings (MeSH)
- Nuller, Yuri. "Effect of naloxone therapy on depersonalization: a pilot stud". Sage. Retrieved 10/8/2011.
- Simeon, Daphne. "An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder". Journal of Clinical Psychopharmacology. Retrieved 2011-10-13.