Articles: narcotic-antagonists.
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Pertussis toxin (PTX) treatment results in ADP-ribosylation of Gi-protein and thus in disruption of mu-opioid receptor signal transduction and loss of the antinociceptive effect of morphine. We have previously demonstrated that pretreatment with ultra-low dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The present study further examined the effect of ultra-low dose naloxone on mu-opioid receptor signaling in PTX-treated rats and the underlying mechanism. ⋯ In addition to the anti-neuroinflammatory effect and glutamate transporter modulation previously observed in PTX-treated rats, the re-establishment of mu-opioid receptor Gi/Go-protein coupling is involved in the restoration of the antinociceptive effect of morphine by ultra-low dose naloxone pretreatment by normalizing the balance between the excitatory and inhibitory signaling pathways. These results show that ultra-low dose naloxone preserves the antinociceptive effect of morphine, suppresses spinal neuroinflammation, and reduces PTX-elevated excitatory Gs-coupled opioid receptors in PTX-treated rats. We suggest that ultra-low dose naloxone might be clinically valuable in pain management.
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Randomized Controlled Trial Multicenter Study Comparative Study
Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose.
Traditionally, the opiate antagonist naloxone has been administered parenterally; however, intranasal (i.n.) administration has the potential to reduce the risk of needlestick injury. This is important when working with populations known to have a high prevalence of blood-borne viruses. Preliminary research suggests that i.n. administration might be effective, but suboptimal naloxone solutions were used. This study compared the effectiveness of concentrated (2 mg/ml) i.n. naloxone to intramuscular (i.m.) naloxone for suspected opiate overdose. ⋯ Concentrated intranasal naloxone reversed heroin overdose successfully in 82% of patients. Time to adequate response was the same for both routes, suggesting that the i.n. route of administration is of similar effectiveness to the i.m. route as a first-line treatment for heroin overdose.
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J. Oral Maxillofac. Surg. · Dec 2009
Randomized Controlled TrialBuprenorphine with bupivacaine for intraoral nerve blocks to provide postoperative analgesia in outpatients after minor oral surgery.
The demonstration that opioid receptors exist in the peripheral nervous system offers the possibility of providing postoperative analgesia in the ambulatory surgical patient. Over the previous decade, many investigators have studied this approach and have compared the efficacy of various opioids added to the local anesthetic near the brachial plexus; and it appears from several of these studies that buprenorphine provides the longest duration of analgesia, the most important parameter of postoperative analgesia in outpatients. One of these studies indicated that the agonist-antagonist, buprenorphine, added to bupivacaine provided a longer period of postoperative analgesia than the traditional opiates, but none of the studies was performed in patients undergoing minor oral surgery to check the efficacy of buprenorphine to provide postoperative analgesia in dental patients. The present study was undertaken to ascertain the efficacy of buprenorphine in providing prolonged postoperative analgesia when added to 0.5% bupivacaine with epinephrine 1:200,000. ⋯ The addition of buprenorphine to the local anesthetic used for intraoral nerve blocks in the present study provided a 3-fold increase in the duration of postoperative analgesia, with complete analgesia persisting 30 hours beyond the duration provided by the local anesthetic alone in 75% of patients. This practice can be of particular benefit to patients undergoing minor oral surgery by providing prolonged analgesia after discharge from the hospital.
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J. Pharmacol. Exp. Ther. · Dec 2009
Nociceptin/orphanin FQ receptor activation attenuates antinociception induced by mixed nociceptin/orphanin FQ/mu-opioid receptor agonists.
Activation of brain nociceptin/orphanin FQ (NOP) receptors leads to attenuation of mu-opioid receptor (MOP receptor)-mediated antinociception. Buprenorphine, a high-affinity partial MOP receptor agonist also binds to NOP receptors with 80 nM affinity. The buprenorphine-induced inverted U-shaped dose-response curve for antinociception may be due to NOP receptor activation, given that, in the presence of the NOP receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J113397), or in NOP receptor knockout mice, buprenorphine has a steeper dose-response curve and acts as a full agonist. ⋯ SB-612111 potentiated antinociception induced by buprenorphine and the other mixed NOP/MOP receptor agonists SR16435 and SR16507. However, SB-612111 had no effect on pentazocine or morphine antinociception, two compounds with no NOP receptor-binding affinity. These results further support the hypothesis that activation of NOP receptors can lead to attenuation of MOP receptor-mediated antinociception elicited by mixed NOP/MOP receptor compounds such as buprenorphine, SR16435, and SR16507 and that, although buprenorphine has low efficacy in vitro, it has significant NOP receptor agonist activity in vivo.
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Suboxone (Buprenorphine/naloxone) is a novel drug used in opiate substitution therapy. In Hungary, it was introduced in November 2007. Suboxone is a product for sublingual administration containing the partial mu-receptor agonist buprenorphine and antagonist naloxone in a 4:1 ratio. ⋯ According to the early experience with Suboxone treatment, it is a well tolerable and successfully applicable drug in the substitution therapy of opiate addicts. A critical phase seems to be the first one or two weeks of treatment. Dropout rate is high during this early period, while after a successful conversion clients presumably remain in therapy for a long period. At the beginning of administration special emphasis must be put on informing patients, especially concerning withdrawal symptoms that might be present during the first week, which highly contributes to better retention in treatment.