ISSN:0272-4391    

DOI:10.1002/ddr.430360302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe effect of 18 traditional Chinese herbal medicines [Kampo medicines (KMs)] on nitric oxide (NO) synthesis in vitro was assessed by using macrophage cell line RAW 264.7 cells. All of the prescriptions enhanced NO synthesis, and eight prescriptions showed strong activity relative to the other remaining prescriptions. After dialysis of the water‐soluble part of the prescriptions, the retaintate showed significant activity, suggesting that macromolecular fractions enhanced NO synthesis. Egg white lysozyme, which can bind to lipopolysaccharide (LPS) and neutralize its biological activities, abrogated NO synthesis of a part of the macromolecular fractions. These results suggest that KM‐stimulated NO synthesis was independent of the contaminated LPS. The NO synthesis was inhibited by NG‐monomethyl‐L‐arginine acetate, an inhibitor of nitric oxide synthase (NOS), showing that induced NO resulted from the activation of inducible NOS but not from nitrite in crude drugs. © 1995 Wiley

ISSN:0272-4391    

DOI:10.1002/ddr.430360303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn order to assess a possible synergistic antinociceptive interactions, the analgesic effects of aspirin per s̀s (acetyl salicylic acid or “ASA”), a nonsteroidal anti‐inflammatory drug (NSAID), and tramadol s.c. (TRA), an atypical opioid analgesic, administered either separately or in combination were determined in a model of pain‐induced functional impairment in the rat, groups of six rats received either vehicle, ASA (175.4, 312.1, 555.1, 987.0, 1, 755.3, or 3, 121.2 μmol/kg) and TRA (21.3, 38.0, 67.5, 120.0, or 213.5 μmol/kg), or a combination of ASA and TRA (24 different combinations). This allowed us to detect the interaction profile of these combinations. The ED50for either ASA or TRA were 1, 173.5 ± 7.4 μmol/kg and 141.5 ± 6.8 μmol/kg, respectively. The data obtained confirmed an interaction between ASA and TRA and showed antinociception that may be additive or synergistic, depending on the drug ratio administered. Furthermore, eight combinations showed various degrees of potentiation (P<.01), whereas the others (16) exhibited analgesic effects not different from that of ASA alone. The combination of ASA (3, 121.2 μmol/kg) and TRA (120.0 μmol/kg) produced the maximum analgesic effect. However, the combination of ASA (987/ μmol/kg) with TRA (120.0 μmo/kg) produced the highest potentiation effects. This study clearly showed (1) that there is an interaction between ASA and TRA and (2) which combination of these analgesic drugs produced either the maximum analgesic effect or the highest degree of potentiation in the rat. © 1

ISSN:0272-4391    

DOI:10.1002/ddr.430360304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIt has been postulated that during liver damage there is an arachidonic acid metabolism deflection toward lipoxygenase products and a simultaneous decrement of the synthesis of cytoprotective prostaglandins. Accordingly, we have demonstrated that leukotriene synthesis inhibition protects the liver from acute damage induced by CCI4. Thus, the aim of the present work was to study the effect of caffeic acid (a specific 5‐lipoxygenase inhibitor) on liver cirrhosis induced by CCI4administration in the rat. Caffeic acid prevented significantly the increment of serum markers of liver damage, as well as lipid peroxidation and the depletion in glycogen content of the liver induced by chronic CCI4intoxication. Collagen content increased fivefold in the CCI4‐treated rats. The group treated with the lipoxygenase inhibitor, in addition to CCI4, showed less collagen content than the group receiving only CCI4(P⩽ .05). Caffeic acid prevented liver damage significantly. The hepatoprotective effect of this compound could be attributed to its ability to inhibit 5‐lipoxygenase activity, and thus leukotriene production. © 1995 Wiley

ISSN:0272-4391    

DOI:10.1002/ddr.430360305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe leumedins, a series of N‐(fluorenyl‐9‐methoxycarbonyl) amino acids, are putative anti‐inflammatory agents that have been shown to inhibit leukocyte recruitment into inflammed tissue. While the exact mechanism of action of these agents is unknown, there are some reports suggesting that leumedins selectively block transmembrane ion flux in neutrophils. In order to examine the possibility that the leumedins may interact with chloride transport mechanisms, we evaluated representative leumedins for their ability to interact with the GABA/benzodiazepine chloride ionophore in rat brain. NPC 17923, at micromolar concentrations, was found to compete for 2 nM [35S]TBPS binding (IC50= 16 μM) and inhibit36CI—influx (IC50= 133 μM) in rat brain. Saturation studies indicated that NPC 17923 inhibited [35S]TBPS binding in a noncompetitive fashion. Other less potent leumedins also inhibited [35S]TBPS binding in a concentration‐dependent fashion. The leumedins had no significant activity at other GABA/benzodiazepine recognition sites labeled by [3H]muscimol, [3H]flunitrazepam, or [3H]RO15‐4513. The two most potent leumedins effectively attenuated36CI—influx into rat brain, while all of the leumedins examined blocked36CI—influx into guinea pig neutrophils at moderate micromolar concentrations. The present data offer the first demonstration that the leumedins can block chloride flux at the rat brain GABA/benzodiazepine chloride ionophore and in guinea pig neutrophils at similar concentrations required to produce anti‐inflammatory actions on human neutrophils. These results show that while the leumedins can block chloride flux in both neurons and neutrophils, the relative low affinity of the leumedins to produce this effect suggests an apparent nonselective interaction at a number of different chloride transporters similar to that found with the disulfonic stilbene derivative chloride channel blockers.

ISSN:0272-4391    

DOI:10.1002/ddr.430360306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn this study, the antinociceptive activity of five non‐steroidal anti‐inflammatory drugs (NSAIDs) was determined in two animal models of different pain intensity and compared with their capacity to produce motor incoordination and death. Intravenous clonixine, diclofenac, dipyrone (metamizole), ketorolac, and piroxicam produced dose‐dependent antinociception in the acetylcholine‐induced writhing test with ED50values ranging from 14 (clonixine) to 205 (dipyrone) μmol/kg. The behavioral responses in the 55°C hot plate assay were also inhibited in a dosedependent manner, but significantly higher doses were required to display antinociceptive activity, the ED50values ranging from 116 (clonixine) to 2, 263 (dipyrone) μmol/kg. In the writhing test, the antinociceptive effects of NSAIDs were present at doses far below those producing toxic effects. In contrast, their ED50values against a more intense nociceptive stimulus approached those producing lethal effects so that the therapeutic ratios were very small, ranging from 1.3 (diclofenac) to 3.0 (dipyrone). The antinociceptive activity of the reference drug morphine is striking, since both types of nociceptive responses were eliminated at doses substantially lower than those producing death (therapeutic ratios of 502 and 121). Morphine exhibited the highest antinociceptive efficacy, followed by dipyrone, ketorolac, clonixine, and piroxicam. Diclofenac showed a more limited efficacy. These findings imply potential risks for patients treated iv with this class of drugs and suggest caution in the use of high doses of NSAIDs. Future development of injectable NSAID formulations should include a detailed analysis of adverse reactions following iv administration of high doses. © 1995 Wile

ISSN:0272-4391    

DOI:10.1002/ddr.430360307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe quinolizinones Ro 19‐5663, Ro 19‐5686 and Ro 41‐3696 bind with high affinity to the benzodiazepine receptor (BZR) in vitro in the rat brain. These compounds exhibit anxiolytic‐like effects in an operant punishment task in mice and rats and anticonvulsant effects by fully protecting against pentylenetetrazol‐induced tonic seizures in mice and rats and fully protecting against audiogenic seizures in genetically susceptible mice. However, they produced at most only minimal motor impairment in the rotarod task in rodents. These compounds attenuated flunitrazepaminduced sleep in squirrel monkeys, thus antagonizing the effects of a BZR full agonist. In a precipitated withdrawal paradigm, chronic oral treatment in seizure‐prone young DBA/2J mice or adult squirrel monkeys was followed by iv challenge with the BZR antagonist sarmazenil. Following the completion of a chronic treatment regiment with high doses of these quinolizinones, no signs of precipitated withdrawal were observed in mice and only weak signs of sarmazenil‐induced withdrawal were observed in monkeys. In contrast, sarmazenil challenge after chronic treatment with the BZR full agonists triazolam and alprazolam elicited marked withdrawal reactions in mice and monkeys, respectively. In sum, these quinolizinones are BZR partial agonists which offer potential anxiolytic and anticonvulsant efficacy concomitant to reduced adverse effects, including a clear reduction of dependence liability, in comparison to BZR full agonists. © 1995 W

ISSN:0272-4391    

DOI:10.1002/ddr.430360308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430360309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430360301

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY