Articles: narcotic-antagonists.
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Drug Alcohol Depend · Sep 1995
Randomized Controlled Trial Comparative Study Clinical TrialCurrent strategies for the treatment of alcohol dependence in the United States.
Substantial progress has been reported in the treatment of patients with alcoholism in the United States. Studies that seek to identify the most appropriate form of therapy for alcohol-dependent patients have been an important part of this effort. Recognition that psychotherapy alone cannot help all patients who have alcoholism has led to interest in the use of pharmacotherapy. Recent research demonstrates that pharmacotherapy with the opioid receptor antagonists naltrexone and nalmefene helps prevent relapse in many alcohol-dependent patients.
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Int J Clin Pharm Th · Sep 1995
Randomized Controlled Trial Clinical TrialRelative bioavailability of controlled-release oral morphine sulfate during naltrexone blockade.
The effect of naltrexone hydrochloride on the bioavailability of 60 mg controlled-release oral morphine sulfate in normal volunteers was determined using a randomized, 2-way crossover, analytically blinded study design. Although naltrexone did not qualitatively alter the concentration-time curve for controlled-release morphine, the area under the plasma morphine concentration-time curve from 0-24 h (AUC0-24) was significantly greater (p < 0.01) for morphine given with naltrexone (265 ng x h/ml) than for morphine given alone (215 ng x h/ml). Compared to morphine given alone, the apparent absorption half-life of morphine was decreased from 0.94-0.58 h (p = 0.01) and Cmax was increased from 28.17 ng/ml to 32.26 ng/ml (p = 0.04) during naltrexone blockade, whereas the Tmax and apparent elimination half-life of morphine were not significantly affected. The minimal differences in morphine bioavailability indicate naltrexone may be useful in comparative bioavailability studies of high-dose opioids in opioid-naive normal volunteers.
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Drug Alcohol Depend · Aug 1995
Clinical Trial Controlled Clinical TrialAssessment of nalmefene glucuronide as a selective gut opioid antagonist.
Opioid use often causes troublesome constipation as a side-effect. Selective antagonism of the intestinal actions of opioids might be useful in the treatment of opioid-induced constipation. ⋯ Oral nalmefene glucuronide precipitated symptoms and signs consistent with the opioid abstinence syndrome in all five subjects a mean of 9.0 h after dosing. We conclude that nalmefene glucuronide does not appear to exert sufficient gut selectivity to be useful in antagonizing constipation due to exogenous opioid administration without antagonizing systemic opioid effects.
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Pharmacol. Biochem. Behav. · Jun 1995
Supersensitivity to opioid analgesics following chronic opioid antagonist treatment: relationship to receptor selectivity.
The effect of chronic opioid antagonist treatment on the analgesic potency of six opioid agonists was compared to changes in opioid receptor density and the selectivity of each agonist for mu (DAMGO), delta (DPDPE) and kappa (U69,593) opioid receptors. Mice were implanted SC with a 15-mg naltrexone or placebo pellet for 8 days. The pellets were removed and 24 h later, mice were sacrificed and binding studies were conducted, or mice were tested in analgesia (tail-flick) dose-response studies. ⋯ There did not appear to be an obvious relationship between receptor selectivity and the magnitude of supersensitivity. These studies indicate that supersensitivity occurs for a broad range of opioid analgesics following chronic opioid antagonist treatment in the mouse. However, the selectivity of these agonists for mu, delta, and kappa receptors does not appear to correlate with differences in supersensitivity.