Naltrexone

It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade. In some countries including the United States, an extended-release formulation is marketed under the trade name Vivitrol.

Also in the US, Methylnaltrexone Bromide, a closely related drug, is marketed as Relistor, for the treatment of Opioid Induced Constipation. It should not be confused with naloxone (which is used in emergency cases of overdose rather than for longer-term dependence control) nor nalorphine.

Both naltrexone and naloxone are full antagonists and will treat an opioid overdose, but naltrexone is longer-acting than naloxone (although neither is an irreversible antagonist like naloxazone), making naloxone a better emergency antidote.


Chemical structure
Naltrexone can be described as a substituted oxymorphone – here the tertiary amine methyl-substituent is replaced with methylcyclopropane.
Naltrexone is the N-cyclopropylmethyl derivative of oxymorphone.
Pharmacology
Naltrexone, and its active metabolite 6-β-naltrexol, are competitive antagonists at μ- and κ-opioid receptors, and to a lesser extent at δ-opioid receptors. The plasma halflife of naltrexone is about 4 hours, for 6-β-naltrexol 13 h. Its mechanism of action in this indication is not fully understood, but as an opioid-receptor antagonist it's likely to be due to the modulation of the dopaminergic mesolimbic pathway which ethanol is believed to activate.
Naltrexone is metabolised mainly to 6β-naltrexol by the liver enzyme dihydrodiol dehydrogenase.These are then further metabolised by conjugation with glucuronide.
Rapid detoxification
Naltrexone is sometimes used for rapid detoxification ("rapid detox") regimens for opioid dependence. The principle of rapid detoxification is to induce opioid-receptor blockage while the patient is in a state of impaired consciousness, so as to attenuate the withdrawal symptoms experienced by the patient.

Rapid detoxification under general anaesthesia involves an unconscious patient and requires intubation and external ventilation. This implant procedure has not been shown scientifically to be successful in "curing" subjects of their addiction, though it does provide a better solution than oral naltrexone for medication compliance reasons.

Naltrexone implants are made by at least three companies, though none have been approved by the U.S. Food and Drug Administration (FDA) or the Australian Therapeutic Goods Administration. There is currently scientific disagreement as to whether this procedure should be performed under local or general anesthesia, due to the rapid, and sometimes severe, withdrawal that occurs from the naltrexone displacing the opiates from the receptor sites.
Rapid detoxification has been criticised by some for its questionable efficacy in long-term opioid dependence management. Rapid detoxification has often been misrepresented as a one-off "cure" for opioid dependence, when it is only intended as the initial step in an overall drug rehabilitation regimen.Rapid detoxification is effective for short-term opioid detoxification, but is approximately 10 times more expensive than conventional detoxification procedures. Aftercare can also be an issue, since at least one well-known center in the United States reported that they will remove an implant from any patient arriving in their facility before admission.
The usefulness of naltrexone in opioid dependence is very limited by the low retention in treatment.

Like disulfiram in alcohol dependence, it temporarily blocks substance intake and does not affect craving. Naltrexone implants have been used successfully in Australia for a number of years as part of a long-term protocol for treating opiate addiction.

Naltrexone treats the physical dependence on opioids, but further psychosocial interventions are often required to enable people to maintain abstinence.
Alcohol dependence
The main use of naltrexone is for the treatment of alcohol dependence. Initial problems of nausea usually disappear after a few days, and other side effects (e.g., heightened liver enzymes) are rare.Naltrexone has two effects on alcohol consumption. The first is to reduce craving while naltrexone is being taken. The second, referred to as the Sinclair Method, occurs when naltrexone is taken in conjunction with normal drinking, and this reduces craving over time.

The first effect only persists while the naltrexone is being taken, but the second persists as long as the alcoholic does not drink without first taking naltrexone.
Depot injectable naltrexone (Vivitrol, formerly Vivitrex, but changed after a request by the FDA) was approved by the FDA on April 13, 2006 for the treatment of alcoholism. This version is made by Alkermes, and will be jointly marketed by Cephalon, Inc.

There has been some controversy regarding the use of opioid-receptor antagonists, such as naltrexone, in the long-term management of opioid dependence due to the effect of these agents in sensitising the opioid receptors. The researchers discovered that Naltrexone improved smoking cessation rates in women by fifty percent, but showed no improvement for men.
Use for Crohn's disease
In a clinical trial conducted by Pennsylvania State University, it was concluded that low dose naltrexone helped people with Crohn's disease, putting the disease into remission in many cases, though it was stated that further study would be required.
Self-injurious behaviors
Some studies suggest that self-injurious behaviors present in developmentally disabled and autistic people can sometimes be remedied with naltrexone. In these cases, it is believed that the self-injury is being done to release beta-endorphin, which binds to the same receptors as heroin and morphine. By removing the "rush" generated by self-injury, the behavior may stop.
Opiate addiction
Naltrexone helps patients overcome urges to abuse opiates by blocking the drugs’ euphoric effects.Some patients do well with it, but the oral formulation, has a drawback: It must be taken daily, and a patient whose craving becomes overwhelming can obtain opiate euphoria simply by skipping a dose before resuming abuse. A preferable alternative for those likely to skip doses is the naltrexone implant, which may be surgically inserted under the skin.

The naltrexone implant appears to be a far more effective means of treating heroin addiction than the oral formulation.
Kleptomania
There are indications that naltrexone might be beneficial in the treatment of kleptomania (compulsive stealing).
Study in overweight and obese patients
Clinical trials are ongoing regarding the use of naltrexone in combination with another drug, bupropion, as a weight loss therapy.
Autism
Dr. https:www.ebs.tga.gov.au/ebs/ANZTPAR/PublicWeb.nsf/cuMedicines?OpenView.