Naltrexone Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
This drug does not have agonistic properties. It is similar to naloxone in terms of pharmacological characteristics; however, it differs in two important ways—long-lasting action
and that its metabolite 6-β-naltrexol is also a strong antagonist. Naltrexone is potentially
hepatotoxic. Naltrexone is used for blocking pharmacological effects of opioids upon their
overdose.
Verwenden
Labeled Naltrexone, intended for use as an internal standard for the quantification of Naltrexone by GC- or LC-mass spectrometry.
Definition
ChEBI: An organic heteropentacyclic compound that is naloxone substituted in which the allyl group attached to the nitrogen is replaced by a cyclopropylmethyl group. A mu-opioid receptor antagonist, it is used to treat alcohol dependence.
Indications
Naltrexone, an orally active opioid receptor antagonist,
restores erectile function in some patients with idiopathic
ED.
Biologische Funktion
Naltrexone (Trexan) is three to five times as potent as
naloxone and has a duration of action of 24 to 72 hours,
depending on the dose. It is used orally in the treatment
of opioid abstinence. Naltrexone exhibits a large firstpass
effect in the liver. However, the major metabolite,
6-β-naltrexol, is also a pure opioid antagonist and contributes
to the potency and duration of action of naltrexone.
Administration of naltrexone orally blocks the
subjective effects of abused opioids and is used to decrease
the craving for opioids in highly motivated recovering
addicts. However, high doses of the opioids
can overcome the naltrexone blockade and lead to
seizures or respiratory depression and death. In addition,
it has been reported recently that naltrexone can
reduce the craving for alcohol in alcoholic patients.
Naltrexone also has been used with success in treating
apneic episodes in children, an effect hypothesized to
be due to blockade of β-endorphin–induced respiratory
depression.
Naltrexone can induce hepatotoxicity at doses only
five times the therapeutic dose and should be used with
care in patients with poor hepatic function or liver damage.
Side effects of the use of naltrexone are more frequently
observed than following naloxone administration.
Such side effects include headache, difficulty
sleeping, lethargy, increased blood pressure, nausea,
sneezing, delayed ejaculation, blurred vision, and increased
appetite.
Allgemeine Beschreibung
Naltrexone is a pure opioid antagonist at allopioid receptor subtypes with the highest affinity for theμ-receptor. Naltrexone is orally bioavailable and blocksthe effects of opiate agonists for approximately 24 hoursafter a single dose of 50 mg. It produces no opioid agonisteffects and is devoid of any intrinsic actions other thanopioid receptor blockade. Theoretically, it should workwell to treat opioid dependence but in clinical practice,patients have shown poor compliance and high relapserates. Naltrexone has also been studied to treat alcohol dependencewith mixed results. To address the complianceissues and effectively remove the “choice” of taking theantagonist, naltrexone was developed into an extendedreleaseinjectable microsphere formulation for IM injectiononce a month (Vivitrol). This formulation providessteady-state plasma concentrations of naltrexone threefoldto fourfold higher than the 50-mg oral dose 4 times aday. Currently, Vivitrol is only indicated for the treatmentof alcohol dependence. A Cochrane review found insufficientevidence from randomized controlled trials toevaluate its effectiveness for treating opioid dependence. Currently, phase II and phase III clinical trials ofan implantable pellet form of naltrexone are being conductedfor treating opioid dependence.
The CYP450 system is not involved in naltrexonemetabolism. Naltrexone is reduced to the active antagonist6-β-naltrexol by dihydrodiol dehydrogenase, a cytosolicenzyme. Naltrexone has a black box warning, because ithas the potential to cause hepatocellular injury when givenin excessive doses.
Biologische Aktivit?t
Naltrexone is derived from oxymorphone and exhibit agonist activity only at doses that are of little clinical significance. In the absence of opioid drugs, naloxone does not cause analgesia, respiratory depression, or sedation. However, when administered with an opioid analgesic, the effects produced by the opioid agonist are promptly reversed. The ability to antagonize opioids at all of the different opioid receptors makes naloxone useful for the treatment of opioid overdose. Naltrexone has a similar profile, but it is orally active and has a significantly longer half-life.
Naltrexone Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
