Articles: narcotic-antagonists.
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Anesthesia and analgesia · Nov 1993
Randomized Controlled Trial Comparative Study Clinical TrialOpioid antagonist adjuncts to epidural morphine for postcesarean analgesia: maternal outcomes.
This prospective, randomized, controlled investigation compared the effects of three prophylactic mu-opioid antagonists, epidural butorphanol (BU) 3 mg, epidural nalbuphine (NB) 10 mg, and oral naltrexone (NX) 6 mg, on postcesarean epidural morphine analgesia. After randomization, 102 term parturients underwent cesarean delivery with epidural anesthesia, 2% lidocaine and epinephrine 1:200,000. ⋯ Through the first 12 h postpartum, the BU group achieved significantly greater analgesia than the morphine sulfate (control) (MS), NB, and NX groups, a significantly lower incidence of severe pruritus than the MS group, and significantly greater satisfaction than MS and NX groups. Epidural morphine and BU promoted better analgesia and satisfaction than any previously documented postcesarean regimen.
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J. Pharmacol. Exp. Ther. · Aug 1993
Evidence for delta opioid receptor subtypes in rat spinal cord: studies with intrathecal naltriben, cyclic[D-Pen2, D-Pen5] enkephalin and [D-Ala2, Glu4]deltorphin.
This study characterized the antinociception produced by intrathecal (i.t.) administration of the respective delta-2 and delta-1 receptor-selective agonists, [D-Ala2, Glu4]deltorphin (DELT) and DPDPE or the mu receptor selective agonist DAMGO in the rat. It also determined whether the antinociception produced by these opioid agonists was differentially affected by i.t. coadministration of the delta-2 receptor-selective antagonist, naltriben (NTB). In the tail-flick test, the ED50 values of DELT and DPDPE were 2.7 micrograms (3.4 nmol) and 19.0 micrograms (29.4 nmol), respectively. ⋯ Although NTB did not antagonize the increase in tail-flick latency produced by 0.1 to 0.3 microgram of DAMGO, it did antagonize the increase produced by 0.03 microgram of DAMGO resulting in a steeper dose-response relationship. Unlike DPDPE or DAMGO, DELT did not increase hot-plate latency except at a dose that produced adverse motor effects. Coadministration of 3 micrograms of NTB antagonized the increase in hot-plate latency produced by DPDPE, but not DAMGO, suggesting that this delta-1 receptor-selective agonist may also have efficacy at delta-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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Dose-responsive motor activity induced by systemic injection of the kappa (kappa) preferring opioid agonist, U50,488H (1-10 mg/kg, s.c.) in guinea pigs was recently reported [Brent P. J. and Bot G. (1992) Psychopharmacology 107: 581-590], characterised at the higher doses used (5-10 mg/kg) by sustained postural abnormalities. The effects on the U50,488H-induced, abnormal, motor response of pharmacological manipulation of opioid receptors and sigma (sigma) sites was studied. ⋯ In addition, haloperidol (1 and 5 mg/kg, s.c.), dextromethorphan (10 mg/kg, s.c.) and DTG (30 mg/kg, s.c.), given in combination with U50,488H, induced behaviour characterised by marked oral activity. In contrast to the effect of haloperidol, pretreatment with the selective dopamine D-2 antagonist, raclopride (10 mg/kg, s.c.), had no significant effect on the abnormal movements induced by U50,488H, but did induce oral activity. These data indicate the possible involvement of kappa opioid receptors in the abnormal movement induced by U50,488H, and further demonstrate that there is an interaction between the kappa receptors and sigma sites which can influence the abnormal motor activity.
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Intrathecally administered mu-opioid (morphine; DAMGO ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin)) and delta-opioid (DPDPE ([D-Pen2,D-Pen5] enkephalin); DADLE ([D-Ala2,D-Leu5]enkephalin)) receptor preferring agonists were systematically challenged with the competitive opiate antagonists naloxone or naltrindole in the rat. Naloxone produced a dose-dependent reduction in agonist effect with the intrathecal IC50 being similar for all agonists (2.1-5.4 micrograms). In contrast, the naltrindole antagonist profile was (IC50 in micrograms) DPDPE (4.0); morphine (23.5); DADLE (> 30) and DAMGO (> 30). Three points are emphasized: (1) antagonism of DPDPE and not DAMGO by naltrindole suggests two distinct opioid sites; (2) a similar potency for naloxone against these agonists suggests that the agonists may act upon spinal sites for which naloxone has comparable affinity or that they may act upon separate sites which are functionally coupled and that the action of naloxone on one or the other site is responsible for the antagonism; and (3) given the modest cross-tolerance between DADLE and mu agonists, the failure of naltrindole to antagonize DADLE suggests that in the rat this peptide acts through a delta site different from that acted upon by DPDPE.
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1. The effects of intrathecal (i.t.) administration of beta-endorphin and two shorter fragments, human and ovine beta-endorphin1-27, were examined for antinociceptive activity in the tail-flick and paw-pressure tests in the rat. Additionally, the ability of ovine beta-endorphin1-27 to influence the action of i.t. beta-endorphin, morphine and [D-Pen2-D-Pen5]enkephalin (DPDPE) was also examined in these tests. 2. ⋯ Administration of ovine beta-endorphin1-27 (1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of morphine (14.9 nmol, i.t.) in both tests and the effect of DPDPE (38.7 nmol) in the tail-flick test. 6. The results show that beta-endorphin1-27 acts as an opioid antagonist at the spinal level in the rat. Its ability to inhibit the action of morphine and DPDPE suggests that it may attenuate beta-endorphin action by an interaction with mu- and/or delta-opioid receptors.