Naltrexone

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Naltrexone
17-(cyclopropylmethyl)-4,5α-epoxy- 3,14-dihydroxymorphinan-6-one
CAS number 16676-29-2 (HCl)	ATC code N07BB04
Chemical formula	C20H23NO4
Molecular weight	341.4
Bioavailability	5-40%
Metabolism	hepatic
Elimination half-life	4 hours (naltrexone), 13 hours (6-β-naltrexol)
Excretion	renal
Pregnancy category	Category B3 (Australia)
Legal status	Schedule 4 (Australia)
Routes of administration	oral

Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed as its hydrochloride salt, naltrexone hydrochloride, under the trade name Revia.

Contents 1 Chemical Structure 2 Pharmacology 3 Rapid detoxification 4 Safety 5 Low Dose Naltrexone (LDN) 5.1 In multiple sclerosis 6 External links 7 References

Chemical Structure

Naltrexone can be described as a substituted oxymorphone – here the tertiary amine methyl-substituent is replaced with methylcyclopropane.

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. This blockade of opioid receptors is the basis behind its action in the management of opioid dependence—it reversibly blocks or attenuates the effects of opioids.

Its use in alcohol (ethanol) dependence has been studied and has been shown to be effective. Its mechanism of action in this indication is not fully understood, but as an opioid-receptor antagonist is likely to be due to the modulation of the dopaminergic mesolimbic pathway which ethanol is believed to activate.

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 blockade 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. Rapid detoxification is also possible under sedation. The rapid detoxification procedure is followed by oral naltrexone daily for up to 12 months for opioid dependence management.

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 management regimen. Rapid detoxification is effective for short-term opioid detoxification, but is approximately 10 times more expensive than conventional detoxification procedures.

Safety

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. That is, after therapy, the opioid receptors continue to have increased sensitivity for a period during which the patient is at increased risk of opioid overdose. This effect reinforces the necessity of monitoring of therapy and provision of patient support measures by medical practitioners.

Low Dose Naltrexone (LDN)

Low Dose Naltrexone (LDN), where the drug is used in doses approximately one-tenth those used for drug/alcohol rehabilitation purposes, is being used by some as an "off-label" experimental treatment for certain immunologically-related disorders. Evidence of safety and efficacy are currently lacking, with no published data from randomised controlled trials in humans. The use of LDN has been pioneered by Dr. Bernard Bihari of New York.

There is some in vitro data that indirectly suggest the potential benefits of LDN therapy. Anecdotal accounts and case reports have also been cited in favour of LDN therapy. Some of the conditions where LDN has been reported as beneficial include multiple sclerosis, Crohn's disease, HIV/AIDS, chronic fatigue syndrome, fibromyalgia, and cancer. Several clinical trials have been planned, with a conference on LDN held in June 2005 in New York.

In multiple sclerosis

Specifically in multiple sclerosis, LDN has been theorized to work in multiple modalities. Without formal studies, there is no formal conclusion as of yet, but the generally accepted theory posited originally by Dr. Bihari is as follows. Dr. Bihari generally observed that multiple sclerosis patients have lower levels of beta-endorphins than healthy controls. Beta-endorphins, in turn, are important regulators of the immune system. The Low Dose Naltrexone dose causes an artificial blockade of the endorphin receptors in the brain. The normal dose of Naltrexone for addiction (~50mg) maintains this blockade continuously, preventing any derived pleasure from taking the forbidden drugs, but the Low Dose of Naltrexone (~3 - 6mgs) is only effective for a short duration. During that time, the body cannot get endorphins to attach to the receptors and apparently overcompensates by creating more. Once the Low Dose Naltrexone dose has been metabolized, the body is left with a "normal" amount of endorphins as compared to healthy controls, which consequently normalizes the immune function. [1]

External links

• Low-dose Naltrexone
  • In multiple sclerosis: Research resources for those on LDN
• LDN Research Trust Website

References

• Armen Berjikly. Low Dose Naltrexone and Multiple Sclerosis. This is MS Multiple Sclerosis Community Encyclopedia. URL accessed on July 30, 2005.

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