Discriminative stimulus effects of acute morphine followed by naltrexone in the squirrel monkey: a further characterization.
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The discriminative stimulus effects of acute morphine followed by naltrexone have been described previously in nonhuman primates. The purposes of this study were to 1) extend the pharmacological characterization of the discrimination by testing mu-opioid agonists other than morphine and opioid-like compounds other than naltrexone and 2) to examine further the relationship between agonist pretreatment time and manifestation of the cue produced by morphine followed by naltrexone. Subjects were trained to discriminate 1.7 mg/kg morphine --> 0.1 mg/kg naltrexone (MOR --> NTX) versus saline followed by 0.1 mg/kg naltrexone. When combined with 0.1 mg/kg naltrexone, all agonists tested, save buprenorphine, meperidine, and nalbuphine, produced dose-dependent increases in MOR --> NTX-appropriate responding, culminating in criterion levels of responding. Comparing agonist ED50 values revealed a rank order of potency of etorphine >> fentanyl >> levorphanol > heroin > or = methadone > or = nalbuphine > or = morphine. ED50 values for buprenorphine and meperidine could not be calculated. MOR --> NTX-appropriate responding after doses of agonist that produced criterion or near criterion levels of responding was also a function of naltrexone dose. After morphine pretreatment, diprenorphine and nalorphine, but not buprenorphine, dose-dependently substituted for naltrexone. The MOR --> NTX discrimination also depended upon the interval between morphine and NTX administration. Finally, 1-h pretreatment with morphine and etorphine, but not buprenorphine, followed by naltrexone generalized to 4 h MOR --> NTX. These results suggest a minimum efficacy requirement of acutely administered agonists together with the naltrexone training dose for stimulus control of behavior. However, in some cases this requirement can be overcome with higher doses of naltrexone. (+info)
Analgesic and antacid properties of i.m. tramadol given before Caesarean section under general anaesthesia.
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BACKGROUND: Intramuscular (i.m.) tramadol increases gastric pH during anaesthesia similar to famotidine. We investigated the antacid analgesic value of a single dose of i.m. tramadol given 1 h before elective Caesarean section performed under general anaesthesia. METHODS: Sixty ASA I parturients undergoing elective Caesarean section were included in a randomized double-blind study. The patients were randomly allocated to receive i.m. tramadol 100 mg (n=30) or famotidine 20 mg (n=30) 1 h before general anaesthesia. RESULTS: At the beginning and the end of anaesthesia, patients receiving tramadol had a median gastric fluid pH of 6.4, which was not significantly different from those treated with famotidine (median 6.3). The infant well-being, as judged by Apgar score, cord blood gas analysis, and neurobehavioural assessment showed no significant difference between the two groups. Nalbuphine consumption in the first 24 h after operation was reduced by 35% in the tramadol group. Pain intensity score on sitting and sedation were significantly greater in famotidine group up to 24 h after surgery. There was no significant difference in incidence and severity of nausea and vomiting between the two groups. CONCLUSION: A single i.m. dose of tramadol is useful pre-treatment to minimize the risk of acid aspiration during operation, and in improving pain relief during 24 h after surgery. (+info)
Characterization and evaluation of silk protein hydrogels for drug delivery.
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The objective of this study was to characterize and evaluate the physicochemical properties and drug release profiles of hydrogels composed of silk protein (SP) polymers. SPs with a low MW (SPL, ca. 18 kDa) and a high MW (SPH, ca. 76 kDa) were used for preparing hydrogels. Both the random coil form and beta-sheet conformation simultaneously existed in the hydrogels according to Fourier-transformed IR determination. Morphologically, the hydrogels showed a sponge-like cross-linked structure produced by physical entanglement as well as chemical hydrogen and covalent bindings. The in vitro buprenorphine delivery from SPH hydrogels showed a slow-release effect, and a zero-order rate was obtained for all preparations. Drug release could be controlled by varying the SPH concentrations or incorporation of SPL into the systems. SP hydrogels showed a stronger barrier property for hydrophilic solutes than for hydrophobic solutes. The incorporation of SPH into Pluronic F-127 (PF-127) hydrogels changed the gel structure from amorphous micelles to a regularly interconnected texture with pores. Furthermore, SPH as an adjuvant polymer in PF-127 and chitosan hydrogels lowered and controlled the amount of drug released from those systems. (+info)
Interactions between an N-methyl-D-aspartate antagonist and low-efficacy opioid receptor agonists in assays of schedule-controlled responding and thermal nociception.
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A growing body of literature has implicated N-methyl-d-aspartate (NMDA) receptor mechanisms in the acute antinociceptive effects of morphine; however, the nature of this interaction has not been thoroughly quantified. Moreover, it is not clear whether NMDA/morphine interactions extend to less efficacious opioids. Therefore, the present study examined the effects of morphine and various low-efficacy opioid agonists in combination with the NMDA antagonist (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959) in two different assays: schedule-controlled responding and thermal nociception. Data were examined with dose-addition analysis to provide a quantitative assessment of the drug interactions. LY235959 and the opioid agonists morphine, buprenorphine, butorphanol, and nalbuphine all decreased rates of schedule-controlled responding. LY235959/morphine and LY235959/buprenorphine mixtures produced additive or subadditive effects in this assay, whereas LY235959/butorphanol and LY235959/nalbuphine mixtures produced additive or supra-additive effects, depending on the relative proportions of each drug in mixture. Morphine, buprenorphine, butorphanol, and nalbuphine also produced dose-dependent antinociception in the assay of thermal nociception, whereas LY235959 failed to produce an effect. In this assay, LY235959 potentiated the antinociceptive effects of morphine and each of the low-efficacy opioids tested. These results suggest that LY235959 may selectively increase the antinociceptive effects of morphine and some low-efficacy opioid receptor agonists without increasing their rate-altering effects. In addition, these data confirm that the behavioral effects of drug mixtures depend on the relative concentrations of the drugs in the mixture and on the endpoint under study. (+info)
Hair analysis by LC-MS as evidence of nalbuphine abuse by a nurse.
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Individuals in any profession can succumb to chemical abuse. Among the healthcare profession, nurses represent a specific group because of their ease of access to drugs, particularly narcotics. Opioids, potentially highly addictive agents, are usually their drug of choice. Nalbuphine, a synthetic opioid analgesic, is prescribed for moderate-to-severe acute pain, for chronic pain syndromes, and in obstetrics to decrease the adverse respiratory effect of opioid epidural administration. The case of a nurse who was suspected of drug misuse after the disappearance of two nalbuphine ampules in an obstetrics service is described. Because of discrepancies in the results of her blood and urine samples, a sample of head hair was subsequently collected from the nurse. A hair analysis of nalbuphine by liquid chromatography-mass spectrometry has not been previously described. Following decontamination and grinding, hair was mixed with a Soerensen buffer, then subjected to ultrasonic treatment (1 h), and extracted with ethyl acetate. A quantitative analysis was performed with two channels (30 and 45 V), and it is based on a m/z 358 for nalbuphine and a m/z 330 for methylclonazepam as an internal standard. The method was linear from 0.020 to 12 ng/mg of hair (R(2) = 0.972), and the limit of detection and limit of quantitation are 0.020 ng/mg. Accuracy (CV), assessed at 0.4 and 1.6 ng/mg of hair, was 6.18% and 5.77%, respectively, for intraday assays and 4.5% and 10.9% for interday assays. Recovery efficiency at 1.6 ng/mg and 8 ng/mg of hair was 100% and 97.4%, respectively. The hair specimen from the nurse (6 cm) was cut into three equal lengths. Nalbuphine, venlafaxine, and nordiazepam were detected. The concentration of nalbuphine was similar in the three hair locks: 5.07, 7.06, and 5.70 ng/mg of hair. A hair analysis revealed the repeated intake of nalbuphine by the nurse. This person was treated for depression for several months with Effexor (venlafaxine) and Nordaz (nordiazepam) prior to the investigation. Hair appears to be a unique matrix to provide evidence for chronic drug exposure by establishing a historic record that is not possible by blood or urine analysis. (+info)
Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers.
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Nalbuphine (Nubain) is a mixed action mu-kappa agonist used clinically for the management of pain. Nalbuphine and other mu-kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, and 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (P=.04) and reached peak levels of 22.1+/-7.1 ng/ml and 54.1+/-11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of "Sick," "Bad" and "Dizzy" were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (P=.05-.0001), and were significantly correlated with increases in PRL (P=.05-.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu- and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol. (+info)
Pharmacological properties of bivalent ligands containing butorphan linked to nalbuphine, naltrexone, and naloxone at mu, delta, and kappa opioid receptors.
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Our investigation of bivalent ligands at mu, delta, and kappa opioid receptors is focused on the preparation of ligands containing kappa agonist and mu agonist/antagonist pharmacophores at one end joined by a chain containing the mu antagonist pharmacophores (naltrexone, naloxone, or nalbuphine) at the other end. These ligands were evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors and their relative efficacy in the [35S]GTPgammaS assay. (+info)
A subanalgesic dose of morphine eliminates nalbuphine anti-analgesia in postoperative pain.
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