Articles: narcotic-antagonists.
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Psychosomatic medicine · Mar 2006
Adrenocortical and nociceptive responses to opioid blockade in hypertension-prone men and women.
Attenuated pain sensitivity and exaggerated adrenocortical stress reactivity have been documented in individuals at high risk for hypertension. The endogenous opioid system may play a role in these response alterations. We compared adrenocortical and nociceptive responses to opioid blockade using naltrexone in hypertension-prone men and women. ⋯ The results are consistent with the inhibitory effects of the endogenous opioids on cortisol response and suggest an altered response timeline among hypertension-prone individuals. The results demonstrate that hypoalgesia may be a marker of hypertension risk in men but not in women.
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J Subst Abuse Treat · Mar 2006
Slow tapering from methadone maintenance in a program encouraging indefinite maintenance.
Longitudinal studies have indicated that most opioid agonist-using patients are not able to successfully complete tapering attempts. Little is known, however, about tapering within a treatment environment that is supportive of indefinite agonist treatment and medication tapering. In this study, all records of patients beginning a slow methadone taper were reviewed (N = 30). ⋯ Patients attempting tapers should be informed about the difficulty involved and be monitored closely for signs of instability. For a few patients, a taper to a lower methadone dose and a switch to buprenorphine/naloxone are obtainable. Program policies that support both tapering attempts and indefinite maintenance are described in this article.
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Randomized Controlled Trial Multicenter Study Comparative Study
Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling.
Pathological gambling is a disabling disorder experienced by approximately 1%-2% of adults and for which there are few empirically validated treatments. The authors examined the efficacy and tolerability of the opioid antagonist nalmefene in the treatment of adults with pathological gambling. ⋯ Subjects who received nalmefene had a statistically significant reduction in severity of pathological gambling. Low-dose nalmefene (25 mg/day) appeared efficacious and was associated with few adverse events. Higher doses (50 mg/day and 100 mg/day) resulted in intolerable side effects.
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Randomized Controlled Trial
Intravenous bolus of ultra-low-dose naloxone added to morphine does not enhance analgesia in emergency department patients.
There is some evidence from in vitro, animal, and postoperative clinical studies that low doses of opioid antagonists combined with morphine increase analgesia. The theoretical model of this effect posits that ultra-low doses of opioid antagonists selectively antagonize excitatory, but not inhibitory, opioid receptor-mediated signaling. To determine whether this effect occurs in emergency department patients presenting with severe acute pain, we conducted a randomized, double-blind placebo-controlled trial to assess the relative analgesic effect of morphine administered with 3 different doses of naloxone versus morphine alone. Patients received 0.1 mg/kg morphine intravenously (IV) over 2 min plus one of 3 different doses of naloxone (0.1 ng/kg, 0.01 ng/kg, or 0.001 ng/kg) or normal saline. A 0 to 10 numerical rating scale (NRS) was used to measure pain intensity at baseline and every 30 min up to 4 hours. One hundred fifty-six patients with a median NRS of 10 (IQR: 8-10) were studied. There were no clinically or statistically significant differences in the mean pain intensity of patients in the 4 treatment groups over the 4-hour study period, nor were there differences in the administration of additional analgesics or incidence of side effects. ⋯ Ultra-low doses of naloxone in the 0.001 ng/kg to 0.1 ng/kg range do not enhance the analgesia provided by morphine alone among emergency department patients with acute, severe pain. This suggests that naloxone in these doses is not an effective adjunct to morphine for control of acute pain.
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Comparative Study
Agonist activity of naloxone benzoylhydrazone at recombinant and native opioid receptors.
1. In the present study, we examined the pharmacological activity of the putative kappa3-opioid receptor agonist naloxone benzoylhydrazone (NalBzoH) at recombinant human opioid receptors individually expressed in Chinese hamster ovary (CHO) cells and native opioid receptors present in rat striatum. 2. At the mu-opioid receptor (MOR), NalBzoH stimulated guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding (pEC50=8.59) and inhibited cyclic AMP accumulation (pEC50=8.74) with maximal effects (Emax) corresponding to 55 and 65% of those obtained with the MOR agonist DAMGO, respectively. ⋯ In rat striatum, NalBzoH enhanced [35S]GTPgammaS binding and inhibited adenylyl cyclase activity. These effects were antagonized by either CTAP, nor-BNI or NTI, each antagonist blocking a fraction of the NalBzoH response. 8. These data demonstrate that NalBzoH displays agonist activity at MOR, DOR and KOR expressed either in a heterologous cell system or in a native environment.