What is Naltrexone?

Naltrexone has a chemical formula of 17- (cyclopropylmethyl) -4,5-epoxy-3,14-dihydroxymorphinan-6-one, a molecular formula of C20H23NO4, and a molecular weight of 341.40100. Treasury, which is incompatible with oxidants, is a pure opioid receptor antagonist, and has a blocking effect on -, -, -opioid receptors. Therefore, it can block the effect of re-drug, thereby weakening the positive strengthening effect and the negative strengthening effect, and plays a good auxiliary role in preventing relapse.

Chinese name: Naltrexone
Foreign name: naltrexone

CAS number: 16590-41-3
Molecular formula: C20H23NO4

Introduction to Naltrexone Compounds

Naltrexone Basic Information

Chinese name: Naltrexone

Chinese alias: 17- (cyclopropylmethyl) -4,5-epoxy-3,14-dihydroxymorphinan-6-one; Naldrone; (5) -17- (Cyclopropylmethyl) -4,5- epoxy-3,14-dihydroxymorphinan-6-one;

English name: naltrexone

English alias: Trexonil; NeMexin; trexan; Depotrex; en1939; celupan; Um-792; Naltrel; en1639; Naltrexone;

CAS number: 16590-41-3

Molecular formula: C ₂₀ H ₂₃ NO ₄

Structural formula:

Molecular weight: 341.40100

Exact mass: 341.16300

PSA: 70.00000 ^[1]

LogP: 1.46330

Naltrexone Physicochemical Properties

Density: 1.47g / cm ³

Melting point: 168-170ºC

Boiling point: 558.1ºC at 760 mmHg

Flash point: 291.4ºC

Refractive index: 1.709

Storage conditions: storehouse is ventilated, low temperature and dry, stored separately from oxidants and food

Vapor pressure: 2.71E-13mmHg at 25 ° C ^[1]

Naltrexone calculated chemical data

1. Hydrophobic parameter calculation reference value (XlogP): None

2.Number of hydrogen-bonded donors: 2

3.Number of hydrogen bond acceptors: 5

4.Number of rotatable chemical bonds: 2

5.Number of tautomers: 6

6.Topological molecular polar surface area: 70

7.Number of heavy atoms: 25

8.Surface charge: 0

9.Complexity: 621

10.Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 4

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 0 ^[2]

14. Uncertain number of chemical bond stereocenters: 0

15.Number of covalent bond units: 1

Naltrexone Pharmacology and Toxicology

Naltrexone Pharmacology

Naltrexone is an opioid receptor anti-antagonist. Its pharmacodynamics are similar to those of naloxone. It can significantly reduce or completely block the opioid receptor, and even reverse the effect caused by intravenous opioids. It can relieve its physical dependence on opioids, so that those who have withdrawn from opioids can maintain a normal life. This product is effective orally, and the effect lasts longer. This product does not cause physical or mental dependence. ^[3]

Naltrexone Toxicology Study

The carcinogenicity study of this product on rats for 2 years proved that the number of vascular tumors in male mesothelioma and bisexuality increased slightly. However, with the exception of a slight increase in female hemangiomas, the incidence of tumors was not different from that in the control group.

Naltrexone hydrochloride was orally administered to rats at 10, 30, and 100 mg / kg / d for 2 years without any signs of toxicity caused by the drug. Naltrexone hydrochloride was administered to rats, dogs, and monkeys at a dose of at least 20 mg / kg. None are toxic. Naltrexone hydrochloride had no teratogenic, mutagenic and carcinogenic toxicity, and no reproductive toxicity. ^[4]

Naltrexone pharmacokinetics

Naltrexone is absorbed quickly and completely after oral administration, reaching its peak in 1 hour, but it is widely metabolized in the liver for the first time, and only 5% enter the blood circulation. The protein binding rate was 20%. The steady-state distribution volume is 16.1 L / kg. The total clearance is about 94L per hour. The main metabolite 6--naltrexol has a slight antagonistic effect. The original drug and metabolites are mainly excreted with urine. No accumulation was seen. ^[3]

Naltrexone indications

1. Blocking dependence on opioids.

2. Adjuvant treatment of alcohol dependent persons. ^[3]

Naltrexone dosage

Naltrexone treatment must be performed when naloxone-induced is negative. Therefore, medication must be used according to the following principles:

Preparation period:
(1) No opioid has been abused within 7 to 10 days before starting medication.
(2) The urine morphine test should be negative. If positive, naltrexone hydrochloride treatment should be postponed until urinary morphine is negative.
(3) Naloxone hydrochloride challenge test before starting medication: After confirming that the urinary morphine test is negative, 0.4-1.2 mg of naloxone hydrochloride is injected subcutaneously or intramuscularly, and the symptoms and signs are observed for 1 hour. If there is no withdrawal symptoms, the challenge test is negative. If positive, naltrexone hydrochloride treatment should be postponed until the challenge test is negative.
Induction period:
Care should be taken to start the treatment slowly and slowly to increase the dose of naltrexone hydrochloride. The induction period is usually 3 to 5 days. The purpose of this period is to make the drug users gradually reach the appropriate dosage of naltrexone hydrochloride. The induction period is performed during hospitalization.
Day 1: Oral naltrexone hydrochloride 2.5mg-5mg. The first dose is usually the most obvious. A severe response indicates that the individual is more dependent on opioids and should be postponed.
The next day: oral 5mg ~ 15mg.
The third day: oral 15mg 30mg.
The fourth day: 30 mg to 40 mg orally.
The fifth day: oral 40mg-50mg.
Maintenance period:
(1) Dose: Take 40mg-50mg orally daily, once a day.
(2) Course of treatment: In principle, as long as there is a possibility of relapse, naltrexone hydrochloride should be taken for prevention. It is recommended to take naltrexone hydrochloride for at least six months. ^[4]

Naltrexone adverse reactions

(1) When the daily dosage of naltrexone reaches 300mg, it can cause liver cell damage.

(2) In addition to liver damage, reactions with an incidence of more than 10% include: difficulty sleeping, anxiety, irritability, abdominal pain / spasm, nausea and / or vomiting, joint muscle pain, and headache.

(3) The reactions with the incidence of adverse reactions below 10% are: loss of appetite, diarrhea, constipation, thirst, and dizziness.

(4) The adverse reactions below 1% are:

Respiratory system: nasal congestion, itching, runny nose, sore throat, excessive mucus, hoarseness, cough, shortness of breath.

Cardiovascular system: epistaxis, phlebitis, edema, elevated blood pressure, non-specific ECG changes, palpitations, and tachycardia.

Gastrointestinal tract: excessive gas production, blood in the stool, diarrhea, ulcers.

Musculoskeletal: Pain, tremor in shoulders, lower limbs and knees.

Skin: oily skin, itching, acne, cold sores.

Genitourinary system: increased urination discomfort and decreased libido.

Mental aspects: depression, forgetfulness, tiredness, restlessness, insanity, hallucinations, nightmares. ^[4]

Naltrexone Taboo

Naltrexone is disabled in the following cases:

(1) Those who use opioid analgesics.

(2) Patients with opioid addiction have not been abstained.

(3) Patients who suddenly stopped opioids.

(4) Naltrexone-induced failure patients.

(5) Those who test positive for opioids.

(6) For those who have a history of allergies to naloxone, it is unclear whether this product is cross-allergic to naloxone or other phenanthrene-containing opioids.

(7) Individuals with acute hepatitis or liver failure. ^[4]

Naltrexone considerations

This product is hepatotoxic and can cause elevated aminotransferases. The dose that causes liver toxicity is only 5 times the amount commonly used in clinical practice, so it should be used with caution for patients with mild liver dysfunction. Liver function should be checked regularly before or after application, preferably once a month.
Dependents who still rely on certain doses of opioids can cause unexpected addiction and severe withdrawal syndrome after taking naltrexone hydrochloride. To avoid withdrawal symptoms or worsening of withdrawal symptoms, patients should be free of opioids for at least 7 to 10 days before naltrexone hydrochloride is administered.
Patients should be warned:
(1) If you try to use opioids while taking naltrexone hydrochloride, you will not experience euphoria in small doses, and severe poisoning symptoms will occur in large doses until coma or death.
(2) Patients taking naltrexone hydrochloride should not use opioid analgesics when they need analgesics in an emergency.
It is necessary to cooperate with the social supervision network and family support system, so that naltrexone hydrochloride can better play an auxiliary role in preventing relapse. ^[4]

Naltrexone for pregnant and lactating women

This product is a class C drug for pregnancy risk. Experiments have shown that a dose of 140 times the clinical dose (approximately 100 mg / kg) may have the effect of killing embryos in rabbits and rats, and can significantly increase the rate of false pregnancy in rats and reduce the pregnancy rate of female rats . There are no reports of fertility effects in humans. It is unknown whether this product can be excreted from the human milk meter. Whether it affects the labor process is also unknown. Therefore, this product should be used with caution in pregnant and lactating women.

Naltrexone for children

The safety of using this product in individuals under 18 years of age has not been identified. ^[4]

Naltrexone Drug Interactions

This product may interfere with the therapeutic effect of opioids. Avoid using opioid analgesics with these drugs at the same time.

Naltrexone overdose

No one has had any experience with overdose. Only one study showed that 800 mg of naltrexone was used daily for 1 week without toxicity. The LD50 of this product in mice, rats and guinea pigs were: 1.100 ± 96mg / kg, (1.450 ± 265) mg / kg and 1.490 ± 102mg / kg. The acute causes of death in mice, rats and dogs are clonic tonic convulsions and respiratory failure.

Due to lack of experience in the treatment of naltrexone excess, symptomatic treatment should be done. ^[4]

Naltrexone Expert Reviews

Naltrexone is an opioid antagonist that can block the binding of exogenous opioids to opioid receptors, and has a blocking effect on all three opioid receptors, significantly reducing or completely blocking the intravenous opioid effect. If used with morphine for a long time, naltrexone can prevent the body's physiological dependence on morphine, and it is likely to have the same effect when used with other opioids. For opioid addicts, naltrexone eliminates its withdrawal symptoms and does not create any dependence or resistance on its own. Clinical studies have shown that 50 mg of naltrexone can block the pharmacological effects of intravenous injection of 25 mg of heroin for 24 hours, and double the dose of naltrexone for 48 hours. ^[3]

Naltrexone withdrawal treatment

(1) The principle of quitting naltrexone: Dopamine levels in the "nucleus accumbens" of the thalamus increase when alcohol-dependent people drink alcohol. One mechanism that causes elevated dopamine levels in the nucleus accumbens is 8-endorphin release, which can directly stimulate dopamine release in the nucleus accumbens, or by inhibiting the activity of 7-aminobutyric acid (GABA) neurons, and The "ventral tegmental area" under the thalamus can indirectly stimulate the release of dopamine, thereby reducing the blocking of dopamine cells. Naltrexone can reverse these two effects, reduce the desire to drink, and consciously control alcohol dependence to stop drinking.

(2) Evidence of alcohol withdrawal from naltrexone: 1383 patients with alcohol dependence who had consciously abstained from alcohol for at least 4 days were included in a study of drug treatment and behavioral interventions for alcohol dependence conducted by 11 universities in the United States. The results showed that : In patients who received drug therapy alone (not behavioral therapy), naltrexone was administered orally daily for OOmg for 16 weeks, which was better than comfort in increasing the percentage of alcohol abstinence days (80.6%) and reducing the risk of alcoholism (66.2%). The dosage group is more effective. The naltrexone treatment group had a better absolute clinical outcome of at least 15% more than the placebo group. Oral naltrexone was significantly better than placebo in preventing recurrence of alcohol abuse after the first abstinence and increasing the percentage of days of abstinence. Agent.

(3) The ideal patient for naltrexone treatment is moderate to severe alcohol dependence. Drink more than 16 days per month; Drink more than 5 servings per drinking day, 1 serving of standard wine equals about 0.15L (5 ounces) of wine, 0.35L (12 ounces) of beer, or 0.04L of spirits ( 1.5 ounces); have alcohol-related problems; have tried to quit alcohol in the past, but failed; still have a motivation to quit at least short-term cessation; have been able to force themselves to quit alcohol before starting naltrexone Days.

(4) Precautions for alcohol withdrawal measures: Before starting naltrexone treatment, the following liver enzymes, ALT, AST, GGT, (glutamyl transferase), and glycosyltransferrin must be measured; No cases of drug abuse. Liver enzymes (ALT, AST, GGT) levels that are 4-5 times higher than normal are relative contraindications for the use of naltrexone. Since naltrexone can block brain opioid receptors, naltrexone should not be used in patients who rely on opioids or patients who need opioids to relieve chronic pain. The commonly used initial dose of naltrexone is 25 mg per day for several days, and then increased to 50 mg per day in about 1 week; it should be taken after meals because nausea and vomiting are prone to be taken on an empty stomach. If the patient has abdominal symptoms, it may be effective to reduce or maintain lower doses plus symptomatic treatment (such as the use of bismuth hyposalicylate). A course of abstinence is 4 months, and liver enzymes should be checked every month.
If the patient can completely quit drinking after treatment, naltrexone can be stopped after 4 months of treatment. Continue monitoring liver enzymes once a month for 4-6 months. If the patient has increased alcohol addiction or started drinking again during the observation period, naltrexone can be re-enabled. If during the course of treatment (3-4 months) occasional alcoholics should consider extending the course of treatment. ^[5]