Abstract:
:AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na(+) channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na(+) channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neuronal death in the penumbra of the ischaemic lesion is suggested to occur by apoptosis, we investigated the ability of AM-36, antioxidants and Na(+) channel antagonists to inhibit toxicity induced by the neurotoxin, veratridine in cultured cerebellar granule cells (CGC's). Veratridine (10 - 300 microM) concentration-dependently reduced cell viability of cultured CGC's. Under the experimental conditions employed, cell death induced by veratridine (100 microM) possessed the characteristics of apoptosis as assessed by morphology, TUNEL staining and DNA laddering on agarose gels. Neurotoxicity and apoptosis induced by veratridine (100 microM) were inhibited to a maximum of 50% by the antioxidants, U74500A (0.1 - 10 microM) and U83836E (0.03 - 10 microM), and to a maximum of 30% by the Na(+) channel blocker, dibucaine (0.1 - 100 microM). In contrast, AM-36 (0.01 - 10 microM) completely inhibited veratridine-induced toxicity ( IC(50) 1.7 (1.5 - 1.9) microM, 95% confidence intervals (CI) in parentheses) and concentration-dependently inhibited apoptosis. These findings suggest veratridine-induced toxicity and apoptosis are partially mediated by generation of ROS. AM-36, which combines both Na(+) channel blocking and antioxidant activity, provided superior neuroprotection compared with agents possessing only one of these actions. This bifunctional profile of activity may underlie the potent neuroprotective effects of AM-36 recently found in a stroke model in conscious rats.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Callaway JK,Beart PM,Jarrott B,Giardina SFdoi
10.1038/sj.bjp.0704018subject
Has Abstractpub_date
2001-04-01 00:00:00pages
1691-8issue
8eissn
0007-1188issn
1476-5381journal_volume
132pub_type
杂志文章abstract::1. The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in a canine model of coronary cyclic flow having some of the characteristics of acute unstable angina. Heparin was studied as a reference anticoagulant. 2. Localized endothelial damage was induced in the circumflex coronary artery ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15460.x
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with...
journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10896.x
更新日期:1980-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Nitric oxide (NO) is known to activate NO-sensitive guanylyl cyclase (NO-GC) and to elicit cGMP production. However, NO has also been proposed to induce cGMP-independent effects. It is accepted practice to use specific NO-GC inhibitors, such as ODQ or NS2028, to assess cGMP-dependent NO effects. ...
journal_title:British journal of pharmacology
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更新日期:2013-09-01 00:00:00
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journal_title:British journal of pharmacology
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abstract::1. Superoxide dismutase (SOD, 60 u ml-1) or ferricytochrome c (70 microM) significantly inhibited thrombin-stimulated platelet adhesion to gelatin-coated plastic, whereas catalase (1000 u ml-1) or mannitol (1 mM) had no effect. 2. The platelet aggregation induced by low concentrations of thrombin (causing less than 45...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12572.x
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abstract::Preclinical and clinical data suggest that a modification in GABA(B) receptor expression and function may contribute to the symptoms of major depression and the response to antidepressants. This includes laboratory animal experiments demonstrating that antidepressants modify brain GABA(B) receptor expression and funct...
journal_title:British journal of pharmacology
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更新日期:2011-01-01 00:00:00
abstract::It is well documented that metabolic syndrome (i.e. a group of risk factors, such as abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides and low cholesterol level in high-density lipoprotein), which raises the risk for heart disease and diabetes, is associated with inc...
journal_title:British journal of pharmacology
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doi:10.1111/bph.12960
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701257
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abstract::1 The effects of diltiazem on smooth muscle cells of the canine basilar artery were investigated by means of microelectrode, double sucrose gap and isometric tension recording methods. 2 The mean membrane potential of the smooth muscle cells was -49.8 mV and they were electrically quiescent. Diltiazem (over 10(-5) M) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09162.x
更新日期:1982-03-01 00:00:00
abstract::1. LP-805, 8-tert-butyl-6,7-dihydropyrrolo-[3,2-e]-5-methylpyrazolo- [1,5a]-pyrimidine-3-carbonitrile, is a newly synthesized potent vasodilator. To investigate the cellular mechanisms of vasorelaxation induced by LP-805, we simultaneously determined the effects of LP-805 on cytosolic Ca2+ concentrations ([Ca2+]i) and...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17121.x
更新日期:1994-12-01 00:00:00
abstract::1. The action of angiotensin on the circular and longitudinal muscle of the human colon has been studied in vitro. The ED50 value (g/ml) of circular muscle was 8.7 x 10(-8) and of longitudinal muscle 3.1 x 10(-8), while the corresponding figures for acetylcholine were 1.6 x 10(-6) and 1.1 x 10(-6), respectively. Angio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09553.x
更新日期:1970-05-01 00:00:00
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb16569.x
更新日期:1988-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2015-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08539.x
更新日期:1973-12-01 00:00:00
abstract::Prostanoids, generated from cyclooxygenase (COX) isoenzymes, play a role in the physiological function of the lower urinary tract and are important mediators of inflammatory hyperalgesia. The present work evaluates the effects of the COX-1/COX-2 inhibitor dexketoprofen as well as of a selective COX-2 inhibitor, NS-398...
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abstract::Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2013-01-01 00:00:00
abstract::1 Neuroprotection has been reported after either activation or blockade of the group I metabotropic glutamate receptor subtype 5 (mGluR5). However, some recent evidence suggests that protection provided by mGluR5 antagonists may reflect their ability to inhibit N-methyl-D-aspartate (NMDA) receptor activity. 2 Here, in...
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更新日期:2005-06-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:1997-07-01 00:00:00
abstract::1.--The small protein Bv8, isolated from the amphibian skin, belongs to a novel family of secreted proteins linked to several biological effects. We describe the expression of Bv8/prokineticins and their receptors in mouse macrophages, and characterize their proinflammatory activities. 2.--The rodent analogue of Bv8, ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706467
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We previously reported that NCX 2057, a compound comprising a nitric oxide (NO)-releasing moiety and the natural antioxidant, ferulic acid (FA), inhibits pro-inflammatory mediators through NO-mediated gene regulation. Here, we have assessed the activities of NCX 2057 in models of inflammatory and...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00324.x
更新日期:2009-09-01 00:00:00
abstract::1. We studied the role of bradykinin (BK) and its active metabolite Des-Arg9-BK on noradrenaline release in association with the incidence of ventricular arrhythmias at reperfusion of the ischaemic myocardium. 2. Experiments were performed in Langendorff perfused isolated hearts of rats subjected to 30 min no flow fol...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb12802.x
更新日期:1993-02-01 00:00:00
abstract::The role of nitric oxide (NO) in striatal dopamine release has been controversial. Most NO synthase inhibitors affect more than one isoform of the enzyme and exert vasoconstrictor effects which may also affect striatal dopamine function. We now report on the effect of a soluble monosodium salt of the selective brain N...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1995-01-01 00:00:00
abstract::Obesity has reached epidemic proportions in the Western society and is increasing in the developing world. It is considered as one of the major contributors to the global burden of disability and chronic diseases, including autoimmune, inflammatory and degenerative diseases. Research conducted on obesity and its compl...
journal_title:British journal of pharmacology
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更新日期:2018-05-01 00:00:00
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更新日期:2008-01-01 00:00:00
abstract::Following the discovery of the first effective antiviral compound (idoxuridine) in 1959, nucleoside analogues, especially acyclovir (ACV) for the treatment of herpesvirus infections, have dominated antiviral therapy for several decades. However, ACV and similar acyclic nucleosides suffer from low aqueous solubility an...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0706446
更新日期:2006-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702580
更新日期:1999-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14052
更新日期:2017-12-01 00:00:00