Abstract：
BACKGROUND AND PURPOSE:Baclofen (a GABA(B) receptor agonist) is the most commonly used anti-spasticity agent in clinical practice. While effective when administered spinally or systemically, the development of progressive tolerance represents a serious limitation for its long-term use. The goal of the present study was to characterize the treatment potency after intrathecal or systemic treatment with the selective AMPA receptor antagonist NGX424 on stretch reflex activity (SRA) and background muscle activity (BMA) in rats with developed baclofen tolerance. EXPERIMENTAL APPROACH:Animals were exposed to 10 min of spinal ischaemia to induce an increase in BMA and SRA. Selected animals were implanted with an intrathecal PE-5 catheter and infused intrathecally with baclofen (1 µg·h⁻¹ ) for 14 days. Before and after baclofen infusion, changes in BMA and SRA were measured at 2 day intervals. After development of baclofen tolerance, the animals were injected intrathecally (1 µg) or subcutaneously (3, 6 or 12 mg·kg⁻¹) with NGX424, and changes in BMA and SRA were measured. KEY RESULTS:Intrathecal or systemic delivery of NGX424 significantly suppressed the BMA and SRA in baclofen-tolerant animals. This effect was dose dependent. The magnitude of BMA and SRA suppression seen after 1 µg (intrathecal) or 12 mg·kg ⁻¹ (s.c.) of NGX424 injection was similar to that seen during the first 5 days of baclofen infusion. CONCLUSIONS AND IMPLICATIONS These data demonstrate that the use of NGX424 can represent an effective therapy to modulate chronic spasticity in patients who are refractory or tolerant to baclofen treatment.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Oshiro M,Hefferan MP,Kakinohana O,Lukacova N,Sugahara K,Yaksh TL,Marsala Mdoi
10.1111/j.1476-5381.2010.00954.xsubject
Has Abstractpub_date
2010-11-01 00:00:00pages
976-85issue
5eissn
0007-1188issn
1476-5381journal_volume
161pub_type
杂志文章abstract：BACKGROUND AND PURPOSE:Biased GPCR ligands are able to engage with their target receptor in a manner that preferentially activates distinct downstream signalling and offers potential for next generation therapeutics. However, accurate quantification of ligand bias in vitro is complex, and current best practice is not a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13441
更新日期：2016-04-01 00:00:00
abstract：:1. gamma-Aminobutyric acid (GABA) was applied by the 'concentration clamp' technique to isolated neurones of Aplysia. GABA induced a chloride current (ICl) due to activation of a single class of chloride-channel. 2. The concentration-response curve for the peak ICl gave an apparent dissociation constant of 6.4 X 10(-5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11718.x
更新日期：1988-11-01 00:00:00
abstract：:1 The actions and interactions of adenosine and dipyridamole were investigated on isolated strips of coronary arteries of beef cattle. It was found that small diameter arteries (about 0.5-1.0 mm o9d.), raised to a moderate level of tone with potassium, responded with relaxation to low concentrations of adenosine. 2 Di...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb06949.x
更新日期：1975-11-01 00:00:00
abstract：:1 The present study comprised treatment of healthy male rats with Delta(9)-tetrahydrocannabinol (THC, 10 mg kg(-1), p.o.), and combinations of THC with benzoflavone moiety (BZF, 10 and 20 mg kg(-1), p.o.) isolated from Passiflora incarnata Linneaus, over a period of 30 days. 2 Upon 30-days chronic administrations, the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705015
更新日期：2003-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Subunit-specific modulators of gamma-aminobutyric acid (GABA) type A (GABA(A)) receptors can help to assess the physiological function of receptors with different subunit composition and also provide the basis for the development of new drugs. Valerenic acid (VA) was recently identified as a beta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00865.x
更新日期：2010-09-01 00:00:00
abstract：:We have studied the effects of the weak bases chloroquine, NH4Cl and amantadine on the handling of certain cardiac glycosides by HeLa cells. When these weak bases are applied acutely to HeLa cells they have only minor effects on the binding of cardiac glycosides to the sodium pumps and on the recovery of pump function...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10532.x
更新日期：1983-08-01 00:00:00
abstract：:1. The NK1 tachykinin receptor agonists, septide, [Sar9,Met(O2)11]SP and [Pro9]SP produced locomotor hyperactivity (10-20 min) when injected intracerebroventricularly (i.c.v.) in the guinea-pig. The most potent in eliciting this hyperactivity was septide (from 0.63 to 5 micrograms), compared to [Sar9,Met(O2)11]SP, whi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15101.x
更新日期：1995-11-01 00:00:00
abstract：:1. The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responses2. After the p...
journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1476-5381.1968.tb07956.x
更新日期：1968-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Intrathecal administration of alpha(2)-adrenoceptor agonists produces potent analgesia. This study addressed the subtype of spinal alpha(2)-adrenoceptor responsible for the analgesic effects of i.t. dexmedetomidine and ST-91 in the formalin behavioural model and their effects on primary afferent ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.341
更新日期：2008-12-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0703691
更新日期：2000-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Dysfunction and injury of endothelial cells in the pulmonary artery play critical roles in the hypertension induced by chronic hypoxia. One consequence of hypoxia is increased activity of 15-hydroxyprostaglandin dehydrogenase (PGDH). Here, we have explored, in detail, the effects of hypoxia on th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12594
更新日期：2014-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17121.x
更新日期：1994-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:K(v)11.1 channels are involved in regulating cellular excitability in various tissues including brain, heart and smooth muscle. In these tissues, at least two isoforms, K(v)11.1a and K(v)11.1b, with different kinetics, are expressed. K(v)11.1 activators are potential therapeutic agents, but their...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00897.x
更新日期：2010-10-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2020-11-03 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14037
更新日期：2017-12-01 00:00:00
abstract：:1 Post-tetanic potentiation (p.t.p.) of the compound action potential in the presence of hexamethonium was observed in the isolated stellate ganglion of the hamster using extracellular postganglionic recordings. 2 The magnitude of the p.t.p. was small (less than a 20% increase) in the control solution, but increased a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07897.x
更新日期：1980-06-01 00:00:00
abstract：:Serotonin 5-HT(7) receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type. The aim of the present study was to assess the expression of native 5-HT(7) receptors and 5-HT(7) receptor mRNA in a...
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0705936
更新日期：2004-10-01 00:00:00
abstract：:1 The mechanism underlying the enhancement by superoxide dismutase (SOD) of endothelium-dependent relaxation was investigated in rabbit mesenteric resistance arteries. 2 SOD (200 U ml(-1)) increased the production of H(2)O(2) in smooth muscle cells (as indicated by the use of an H(2)O(2)-sensitive fluorescent dye). 3 ...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0705255
更新日期：2003-05-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb14986.x
更新日期：1995-06-01 00:00:00
abstract：:1. Carrageenin or 5-hydroxytryptamine-induced oedema of the mouse hind paw was antagonized by catecholamines acting on both alpha- and beta-adrenoceptors.2. Increased permeability of the mouse peritoneum induced by the local injection of acetic acid or pro-inflammatory mediators was antagonized by catecholamines actin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08086.x
更新日期：1972-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
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更新日期：2004-08-01 00:00:00
abstract：:1. Orexin-containing neurons have been implicated in feeding, sleep-wake cycles and more recently in drug-seeking behaviour. 2. Pretreatment of alcohol-preferring (iP) rats with an orexin1 receptor antagonist (SB-334867, 20 mg kg(-1), intraperitoneally) completely abolished an olfactory cue-induced reinstatement of al...
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更新日期：2006-07-01 00:00:00
abstract：:1 The beta-adrenoceptor agonist isoprenaline normally causes only a small and inconsistent increase in the membrane potential of cells in guinea-pig liver slices, in contrast to the large hyperpolarizations seen with alpha-agonists. However, after a selective alpha-adrenoceptor agonist has been applied, the response t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb06991.x
更新日期：1977-01-01 00:00:00
abstract：:In the mammalian CNS, glutamate is the major excitatory neurotransmitter. Ionotropic glutamate receptors (iGluRs) are responsible for the glutamate-mediated postsynaptic excitation of neurons. Regulation of glutamatergic synapses is critical for higher brain functions including neural communication, memory formation, ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15050
更新日期：2020-03-11 00:00:00
abstract：:There are proposals for the implementation of beta(2)-adrenoceptor agonists for the management of muscle wasting diseases. The idea has been initiated by studies in animal models which show that beta(2)-adrenoceptor agonists cause hypertrophy of skeletal muscle. Their use in clinical practice will also need an underst...
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pub_type： 杂志文章
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更新日期：2006-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0702607
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：10.1038/bjp.2008.28
更新日期：2008-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Orally administered withanoside IV (a compound isolated from the roots of Withania somnifera) improved memory deficits in mice with a model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35). Sominone, an aglycone of withanoside IV, was identified as an active metabolite after ora...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00313.x
更新日期：2009-08-01 00:00:00
abstract：:1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12355.x
更新日期：1991-08-01 00:00:00
abstract：:In this issue, BJP is proud to publish an Endothelium Themed Section to celebrate the life of Robert F. Furchgott, who died on May 19th 2009. It is 30 years since he discovered endothelium-derived relaxant factor and a decade since he was awarded the Nobel Prize for this work. His discovery has led to an array of new ...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/j.1476-5381.2009.00366.x
更新日期：2009-06-01 00:00:00
