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Mg/kg Morphine (kg + morphine)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Conditional involvement of striatal serotonin3 receptors in the control of in vivo dopamine outflow in the rat striatum

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003
Grégory Porras
Abstract Serotonin3 (5-HT3) receptors can affect motor control through an interaction with the nigrostriatal dopamine (DA) neurons, but the neurochemical basis for this interaction remains controversial. In this study, using in vivo microdialysis, we assessed the hypothesis that 5-HT3 receptor-dependent control of striatal DA release is conditioned by the degree of DA and/or 5-HT neuron activity and the means of DA release (impulse-dependent vs. impulse-independent). The different DA-releasing effects of morphine (1 and 10 mg/kg), haloperidol (0.01 mg/kg), amphetamine (1 and 2.5 mg/kg), and cocaine (10 and 20 mg/kg) were studied in the striatum of freely moving rats administered selective 5-HT3 antagonists ondansetron (0.1 mg/kg) or MDL 72222 (0.03 mg/kg). Neither of the 5-HT3 antagonists modified basal DA release by itself. Pretreatment with ondansetron or MDL 72222 reduced the increase in striatal DA release induced by 10 mg/kg morphine but not by 1 mg/kg morphine, haloperidol, amphetamine or cocaine. The effect of 10 mg/kg morphine was also prevented by intrastriatal ondansetron (1 µm) administration. Reverse dialysis with ondansetron also reduced the increase in DA release induced by the combination of haloperidol and the 5-HT reuptake inhibitor citalopram (1 mg/kg). Considering the different DA and 5-HT-releasing properties of the drugs used, our results demonstrate that striatal 5-HT3 receptors control selectively the depolarization-dependent exocytosis of DA only when central DA and 5-HT tones are increased concomitantly. [source]

Differential roles of corticotropin-releasing factor receptor subtypes 1 and 2 in opiate withdrawal and in relapse to opiate dependence

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2000
Lin Lu
Abstract The possible effects on the morphine withdrawal signs of the nonspecific corticotropin-releasing factor (CRF) receptor antagonist ,-helical CRF, the selective CRF receptor subtype 1 antagonist CP-154,526 and the selective CRF receptor subtype 2 antagonist antisauvagine-30 (AS-30) were investigated in rats. The most withdrawal signs, including jumping, teeth chatter, writhing, shakes, lacrimation, piloerection, irritability and diarrhoea, were attenuated by pretreatment with ,-helical CRF (10 µg i.c.v.) and CP-154,526 (30 mg/kg i.p.). However, no morphine withdrawal signs except for diarrhea were significantly affected by pretreatment with AS-30 (10 µg, i.c.v.). To investigate the possible role of different CRFR antagonists (,-helical CRF, CP-154,526 and AS-30) in relapse to opiate dependence, the 28-day extinction of morphine-conditioned place preference (CPP) was used. The morphine-CPP disappeared following a 28-day extinction and then was reactivated by a single injection of 10 mg/kg morphine. Pretreatment with ,-helical CRF (10 µg, i.c.v.) and CP-154,526 (30 mg/kg, i.p.) could significantly block this reactivation of morphine-CPP. In contrast, pretreatment with AS-30 (1 or 10 µg i.c.v.) did not affect this reactivation of morphine-CPP. The present study demonstrated that activation of the CRF receptor is involved in morphine withdrawal signs and relapse to morphine dependence, and that the role of CRF receptor subtypes 1 and 2 in withdrawal and reactivation of morphine dependence is not identical. CRF receptor subtype 1, but not subtype 2, is largely responsible for the action of the CRF system on opiate dependence. These results suggest that the CRF receptor antagonists, particularly the CRF receptor subtype 1 antagonist, might be of some value in the treatment and prevention of drug dependence. [source]

Synergistic Interactions Between a KCNQ Channel Opener and an Opioid: Flupirtine and Morphine in Rat Pain Models Including Neuropathic Pain

PAIN MEDICINE, Issue 7 2007
C Goodchild
Purpose of the study:, Flupirtine is an established clinical analgesic for mild to moderate musculoskeletal pain states. It has recently been shown to be a KCNQ 2,3 potassium channel opener. These experiments were performed to see if this property could be useful in treating more severe pain states characterised by central sensitisation with the drug either given alone or in combination with morphine. Methods:, Experiments were performed in rats in an observer blinded fashion with vehicle controls. Non sedating doses of flupirtine, morphine and combinations containing both drugs were defined using the rotarod technique. Dose response relationships were determined for non sedating doses of both drugs given alone and together in combination in causing antinociception in three nociception paradigms: electrical pain; carrageenan paw inflammation; streptozotocin-induced diabetic neuropathy. Results:, Flupirtine and morphine when given alone caused slight to moderate antinociception in all three paradigms. Flupirtine also caused significant increases in morphine antinociception in all three models. In carrageenan paw inflammation complete reversal of carrageenan-induced hyperalgesia was caused by 10 mg/kg flupirtine in combination with 0.4 mg/kg morphine. These doses of the two drugs were ineffective when given alone but the combination caused complete antinociception in this model of inflammatory pain. In the diabetic neuropathy model (see figure) morphine 3.2 mg/kg given alone caused significant antinociception but the size of that response was significantly less than that caused by a lower dose of morphine (1.6 mg/kg shown to be ineffective when it was given alone) given in combination with flupirtine 10 mg/kg (p < 0.001; one way ANOVA). Conclusions:, Flupirtine should be investigated as an adjunct analgesic with opioids for the management of patients with severe pain states involving central sensitization. [source]

Oral versus Intravenous Opioid Dosing for the Initial Treatment of Acute Musculoskeletal Pain in the Emergency Department

ACADEMIC EMERGENCY MEDICINE, Issue 12 2008
James R. Miner MD
Abstract Objectives:, The objective was to compare the time to medication administration, the side effects, and the analgesic effect at sequential time points after medication administration of an oral treatment strategy using oxycodone solution with an intravenous (IV) treatment strategy using morphine sulfate for the initial treatment of musculoskeletal pain in emergency department (ED) patients. Methods:, This was a prospective randomized clinical trial of patients >6 years old who were going to receive IV morphine sulfate for the treatment of musculoskeletal pain but did not yet have an IV. Consenting patients were randomized to have the treating physician order either 0.1 mg/kg morphine sulfate IV or 0.125 mg/kg oxycodone orally in a 5 mg/5 mL suspension as their initial treatment for pain. The time from the placement of the order to the administration of the medication was recorded. Pain was measured using a 100-mm visual analog scale (VAS) and recorded at 0, 10, 20, 30 and 40 minutes after drug administration. Results:, A total of 405 eligible patients were identified during the study period; 328 (81.0%) patients consented to be in the study. A total of 158 patients were randomized to the IV morphine sulfate treatment group, and 162 were randomized to the oral oxycodone treatment group. Of the patients who were randomized to IV therapy, 34 were withdrawn from the study prior to drug administration; leaving 125 patients in the IV group for analysis. Of the patients who randomized to oral therapy, 22 were withdrawn from the study prior to drug administration, leaving 140 patients for analysis. No serious adverse events were detected. There was a 12-minute difference between the median time of the order and the administration of oral oxycodone (8.5 minutes) and IV morphine (20.5 minutes). The mean percent change in VAS score was larger for patients in the IV therapy group than those in the oral therapy group at 10 and 20 minutes. At 30 and 40 minutes, the authors could no longer detect a difference. The satisfaction scale score was higher after treatment for the morphine group (median = 4; interquartile range [IQR] = 4 to 5) than for the oxycodone group (median = 4; IQR = 2 to 5; p = 0.008). Conclusions:, The oral loading strategy was associated with delayed onset of analgesia and decreased patient satisfaction, but a shorter time to administration. The oral loading strategy using an oxycodone solution provided similar pain relief to the IV strategy using morphine 30 minutes after administration of the drug. Oral 0.125 mg/kg oxycodone represents a feasible alternative to 0.1 mg/kg IV morphine in the treatment of severe acute musculoskeletal pain when difficult or delayed IV placement greater than 30 minutes presents a barrier to treatment. [source]