A new class of potent centrally acting muscle relaxants: pharmacology of oxazolidinones in rat decerebrate rigidity.

Abstract:

:The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-phenyl-1,3-oxazolidin-2-on e (MLV-6976) being the most potent. In addition to the oxazolidinones, an aminoalcohol derivative, (1RS,2SR)-5-methyl-1-phenyl-2-(3-piperidinopropylamino )hexan-1-ol (MLV-5860) also reduced the rat decerebrate rigidity. In the oxazolidinone series, the optical isomers with absolute configuration (S) at the 4-position were more potent than the corresponding (4R)-isomers, while there was no significant difference in their LD50 values. Normal rats and mice receiving MLV-6976 at doses which reduced decerebrate rigidity showed no behavioural changes, impairment of motor coordination only appearing at extremely high doses. MLV-6976 and its derivatives did not affect spinal reflex potentials in cats. MLV-6976 reduced the severity of harmaline-induced tremor in mice in a dose-dependent manner, but slightly augmented tremorine-induced tremor. The frequency of the spike discharges induced by iontophoretically applied glutamate was reduced by MLV-6976 in a dose-dependent manner in rat cortical neurones. The amplitude of miniature endplate potentials of the rat diaphragm was decreased by MLV-6976 only at concentrations greater than 0.1 mM. It is concluded that MLV-6976 acts on the brainstem or/and higher levels of the brain rather than on the spinal cord or the peripheral nervous system to reduce the excessive activities of the nervous system.

journal_name

Br J Pharmacol

authors

Masaki M,Shinozaki H

doi

10.1111/j.1476-5381.1986.tb11138.x

subject

Has Abstract

pub_date

1986-09-01 00:00:00

pages

219-28

issue

1

eissn

0007-1188

issn

1476-5381

journal_volume

89

pub_type

杂志文章
  • Contractile effects by intracellular angiotensin II via receptors with a distinct pharmacological profile in rat aorta.

    abstract::1. We studied the effect of intracellular angiotensin II (Ang II) and related peptides on rat aortic contraction, whether this effect is pharmacologically distinguishable from that induced by extracellular stimulation, and determined the Ca2+ source involved. 2. Compounds were delivered into the cytoplasm of de-endoth...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702421

    authors: Brailoiu E,Filipeanu CM,Tica A,Toma CP,de Zeeuw D,Nelemans SA

    更新日期:1999-03-01 00:00:00

  • Changes in the cytosolic Ca2+ concentration and Ca(2+)-sensitivity of the contractile apparatus during angiotensin II-induced desensitization in the rabbit femoral artery.

    abstract::1. To investigate the underlying mechanism for the angiotensin II-induced desensitization of the contractile response during the prolonged stimulation of the vascular smooth muscle, we determined the effects of angiotensin-II on (1) cytosolic Ca2+ concentration ([Ca2+]i) and tension using fura-2-loaded medial strips o...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0703092

    authors: Ushio-Fukai M,Yamamoto H,Toyofuku K,Nishimura J,Hirano K,Kanaide H

    更新日期:2000-02-01 00:00:00

  • The cholinergic properties of some amino-acid esters and amides.

    abstract::1. Several amino-acid esters and amides have been prepared and their toxicological and pharmacological properties have been investigated. Some of the quaternary esters and amides were lethal to mice at doses below 1 mg/kg; this lethality was usually associated with high nicotinic activity. None of the compounds showed...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1968.tb07056.x

    authors: Barrass BC,Brimblecombe RW,Parkes DC,Rich P

    更新日期:1968-10-01 00:00:00

  • Protective effects of ranolazine in guinea-pig hearts during low-flow ischaemia and their association with increases in active pyruvate dehydrogenase.

    abstract::1. In isolated Langendorff-perfused, electrically-paced, hearts of guinea-pigs, global low-flow-ischaemia (LFI; at 0.7 ml min-1) resulted in marked increases in the rates of release of lactate, lactate dehydrogenase (LDH) and creatine kinase (CK) over a 30 min period. At the end of the LFI period, tissue ATP content w...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1993.tb13637.x

    authors: Clarke B,Spedding M,Patmore L,McCormack JG

    更新日期:1993-07-01 00:00:00

  • The ABCG family of membrane-associated transporters: you don't have to be big to be mighty.

    abstract::Along with many other mammalian ATP-binding cassette (ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding proteins ranging from 638 to 678 amino acids in length. All f...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1476-5381.2010.01177.x

    authors: Kerr ID,Haider AJ,Gelissen IC

    更新日期:2011-12-01 00:00:00

  • A prolyl oligopeptidase inhibitor, KYP-2047, reduces α-synuclein protein levels and aggregates in cellular and animal models of Parkinson's disease.

    abstract:BACKGROUND AND PURPOSE:The aggregation of α-synuclein is connected to the pathology of Parkinson's disease and prolyl oligopeptidase (PREP) accelerates the aggregation of α-synuclein in vitro. The aim of this study was to investigate the effects of a PREP inhibitor, KYP-2047, on α-synuclein aggregation in cell lines ov...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2012.01846.x

    authors: Myöhänen TT,Hannula MJ,Van Elzen R,Gerard M,Van Der Veken P,García-Horsman JA,Baekelandt V,Männistö PT,Lambeir AM

    更新日期:2012-06-01 00:00:00

  • Local anaesthetic and anti-arrhythmic actions of alprenolol relative to its effect on intracellular potentials and other properties of isolated cardiac muscle.

    abstract::1. Alprenolol, a beta-adrenoceptor blocking drug reported to have the same potency as propranolol in vitro and in vivo, was found to be four times more active than procaine as a local anaesthetic on frog sciatic nerve.2. At doses of 0.125 mg/kg and above alprenolol protected anaesthetized guinea-pigs against ouabain-i...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1970.tb09884.x

    authors: Singh BN,Williams EM

    更新日期:1970-04-01 00:00:00

  • Inflammasomes: a novel therapeutic target in pulmonary hypertension?

    abstract::Pulmonary hypertension (PH) is a rare, progressive pulmonary vasculopathy characterized by increased mean pulmonary arterial pressure, pulmonary vascular remodelling and right ventricular failure. Current treatments are not curative, and new therapeutic strategies are urgently required. Clinical and preclinical eviden...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.14375

    authors: Scott TE,Kemp-Harper BK,Hobbs AJ

    更新日期:2019-06-01 00:00:00

  • The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory.

    abstract:BACKGROUND AND PURPOSE:There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.01143.x

    authors: Wang W,Wang F,Yang YJ,Hu ZL,Long LH,Fu H,Xie N,Chen JG

    更新日期:2011-03-01 00:00:00

  • The actions of a new beta-adrenoceptor blocking drug, ICI 66082, on the rabbit papillary muscle and on the dog heart.

    abstract::1 The actions of 4-(2-hydroxy-3-isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new beta-adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.2 ICI 66082 (up to 1 mg/ml) did not...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1974.tb09644.x

    authors: Harry JD,Knapp MF,Linden RJ

    更新日期:1974-06-01 00:00:00

  • Investigating interactions between epicardial adipose tissue and cardiac myocytes: what can we learn from different approaches?

    abstract::Heart disease is a major cause of morbidity and mortality throughout the world. Some cardiovascular conditions can be modulated by lifestyle factors such as increased exercise or a healthier diet, but many require surgical or pharmacological interventions for their management. More targeted and less invasive therapies...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bph.13678

    authors: Rietdorf K,MacQueen H

    更新日期:2017-10-01 00:00:00

  • Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin-resistant rats.

    abstract:BACKGROUND AND PURPOSE:Insulin resistance is often found to be associated with high blood pressure. We propose that in insulin-resistant hypertension, endothelial dysfunction is the consequence of increased activity of vascular MMP-2. As MMP-2 proteolytically cleaves a number of extracellular matrix proteins, we hypoth...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2011.01583.x

    authors: Nagareddy PR,Rajput PS,Vasudevan H,McClure B,Kumar U,Macleod KM,McNeill JH

    更新日期:2012-02-01 00:00:00

  • Potassium channel openers, NIP-121 and cromakalim, enhance the relaxation induced by sodium nitroprusside in the guinea-pig isolated trachea.

    abstract::1. The effect of the potassium channel openers, NIP-121 and cromakalim, on agonist-induced relaxation of the guinea-pig isolated trachea was investigated and the results were compared with those in the epithelium-denuded trachea. 2. Tracheal strips were incubated with a potassium channel opener or vehicle for 30 min i...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1992.tb13416.x

    authors: Shikada K,Tanaka S

    更新日期:1992-12-01 00:00:00

  • The influence of an extraneuronal compartment on the relaxation of the cat nictitating membrane in vivo.

    abstract::1 Contractions of the cat nictitating membrane were elicited on stimulation of the internal carotid nerve, and the effects were studied of desipramine and two inhibitors of catechol-O-methyltransferase, U-0521 and pyrogallol, on the subsequent relaxation of the muscle. 2 The relaxation of the nictitating membrane occu...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1978.tb07762.x

    authors: Eccles R,Maclean AG

    更新日期:1978-04-01 00:00:00

  • Selective depletion of noradrenaline: a proposed mechanism of the adrenergic neurone-blocking action of bretylium.

    abstract::1. The effects of bretylium have been investigated on the content and sub-cellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline in response to stimulation of the splenic nerve.2. Bretylium, 15 min after its administration, produces a significant depletion of noradrenaline in only th...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1970.tb09887.x

    authors: Abbs ET,Robertson MI

    更新日期:1970-04-01 00:00:00

  • Studies on RX 781094: a selective, potent and specific antagonist of alpha 2-adrenoceptors.

    abstract::1 The selectivity and specificity of RX 781094 [2-(2-(1,4 benzodioxanyl))2-imidazoline HCl] for alpha-adrenoceptors have been examined in peripheral tissues. 2 In isolated tissue experiments RX 781094 was a competitive antagonist at prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of the...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1983.tb08809.x

    authors: Doxey JC,Roach AG,Smith CF

    更新日期:1983-03-01 00:00:00

  • Alterations of insulin secretion from mouse islets treated with sulphonylureas: perturbations of Ca2+ regulation prevail over changes in insulin content.

    abstract::1. To determine how pretreatment with sulphonylureas alters the beta cell function, mouse islets were cultured (18 - 20 h) without (controls) or with (test) 0.01 microM glibenclamide. Acute responses to glucose were then determined in the absence of glibenclamide. 2. Test islets were insensitive to drugs (sulphonylure...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0702731

    authors: Anello M,Gilon P,Henquin JC

    更新日期:1999-08-01 00:00:00

  • Blood pressure reflexes following activation of capsaicin-sensitive afferent neurones in the biliopancreatic duct of rats.

    abstract::1. Inflammatory diseases of the pancreas or diseases which cause obstruction within the biliary or within the biliary or pancreatic duct system are associated with severe pain. Although neuropeptides such as substance P are present in the biliary tree, only few capsaicin-sensitive, substance P-positive nerve fibres ha...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1994.tb14772.x

    authors: Griesbacher T

    更新日期:1994-02-01 00:00:00

  • An effect of haloperidol on the increased food and water intake induced in rabbits by 2-deoxy-D-glucose.

    abstract::Rabbits treated with 2-deoxy-D-glucose (2DG) (300 mg/kg) show an increased intake of food and water. Pretreatment with haloperidol (1 mg/kg) abolishes the increase in water intake but does not prevent the increase in food intake. ...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:

    authors: Anderson J,Sharman DF,Stephens DB

    更新日期:1979-05-01 00:00:00

  • Glycogen synthase kinase 3: more than a namesake.

    abstract::Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1476-5381.2008.00085.x

    authors: Rayasam GV,Tulasi VK,Sodhi R,Davis JA,Ray A

    更新日期:2009-03-01 00:00:00

  • Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids attenuate early occurrence of nonalcoholic fatty liver disease.

    abstract:BACKGROUND AND PURPOSE:The ω-3 polyunsaturated fatty acids (PUFAs) mediate protective effects on several metabolic disorders. However, the functions of their metabolites in the early stage of nonalcoholic fatty liver disease (NAFLD) are largely unknown. EXPERIMENTAL APPROACH:Mice were fed a control diet, high-fat diet...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.13844

    authors: Wang C,Liu W,Yao L,Zhang X,Zhang X,Ye C,Jiang H,He J,Zhu Y,Ai D

    更新日期:2017-07-01 00:00:00

  • The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.

    abstract:BACKGROUND AND PURPOSE:beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally i...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2010.00656.x

    authors: Kurz C,Ungerer I,Lipka U,Kirr S,Schütt T,Eckert A,Leuner K,Müller WE

    更新日期:2010-05-01 00:00:00

  • Modulation by prednisolone of calcium handling in skeletal muscle cells.

    abstract::1. Increased calcium (Ca2+) influx has been incriminated as a potential pathological mechanism in the chronic skeletal muscle degeneration exhibited by Duchenne muscular dystrophy (DMD) patients. We have studied the influence of the glucocorticoid alpha-methylprednisolone (PDN), the only drug known to have a beneficia...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1995.tb15930.x

    authors: Metzinger L,Passaquin AC,Leijendekker WJ,Poindron P,Rüegg UT

    更新日期:1995-12-01 00:00:00

  • Rho kinase inhibitor fasudil reduces l-DOPA-induced dyskinesia in a rat model of Parkinson's disease.

    abstract:BACKGROUND AND PURPOSE:Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l-DOPA-induced d...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/bph.15275

    authors: Lopez-Lopez A,Labandeira CM,Labandeira-Garcia JL,Muñoz A

    更新日期:2020-12-01 00:00:00

  • Augmentation of allergic inflammation in prostanoid IP receptor deficient mice.

    abstract::1 To evaluate the role of prostaglandin I(2) (PGI(2)) in allergic inflammation, allergic responses in the airway, skin and T cells were studied in mice lacking the receptor for PGI(2) (the prostanoid IP receptor) through gene disruption. 2 Three inhalations of antigen caused an increase in plasma extravasation, leukoc...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0704872

    authors: Takahashi Y,Tokuoka S,Masuda T,Hirano Y,Nagao M,Tanaka H,Inagaki N,Narumiya S,Nagai H

    更新日期:2002-10-01 00:00:00

  • Tyr-c[D-Orn-Tyr(Bzl)-Pro-Gly]: a novel antiproliferative acting somatostatin receptor agonist with mu-opioid receptor-sensitizing properties.

    abstract::(1) Here, we introduce a beta-casomorphin-5-derived cyclic pentapeptide, cCD-2 (Tyr-cyclo[d-Orn-Tyr(Bzl)-Pro-Gly]), which inhibits the cell growth of a variety of human cancer cell lines. (2) This opioid-derived peptide possesses only low affinity for mu-receptors, but enhances the agonist binding to mu-receptors in v...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0705416

    authors: Stirnweiss J,Hartrodt B,Greksch G,Stürzebecher U,Böhmer FD,Neubert K,Liebmann C

    更新日期:2003-09-01 00:00:00

  • Inhibition of Na+/H+-exchanger with sabiporide attenuates the downregulation and uncoupling of the myocardial beta-adrenoceptor system in failing rabbit hearts.

    abstract::Chronic heart failure (HF) is characterized by left ventricular (LV) structural remodeling, impaired function, increased circulating noradrenaline (NA) levels and impaired responsiveness of the myocardial beta-adrenoceptor (betaAR)-adenylyl cyclase (AC) system. In failing hearts, inhibition of the sodium/proton-exchan...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706714

    authors: Leineweber K,Aker S,Beilfuss A,Rekasi H,Konietzka I,Martin C,Heusch G,Schulz R

    更新日期:2006-05-01 00:00:00

  • Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve.

    abstract:BACKGROUND AND PURPOSE:Amitriptyline is often prescribed as a first-line treatment for neuropathic pain but its precise mode of analgesic action remains uncertain. Amitriptyline is known to inhibit voltage-dependent ion channels and also to act as an antagonist at ligand-gated ion channels, such as nicotinic acetylchol...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.2009.00347.x

    authors: Freysoldt A,Fleckenstein J,Lang PM,Irnich D,Grafe P,Carr RW

    更新日期:2009-10-01 00:00:00

  • The dependence of excitatory junction potential amplitude on the external calcium concentration in narcotic tolerant mouse vas deferens.

    abstract::The dependence of neurotransmitter secretion on external calcium ions during development of opiate tolerance in the mouse vas deferens was studied. The writhing response of mice to an i.p. injection of acetylcholine was inhibited by morphine. Reversal of this antinociceptive effect of morphine during chronic treatment...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1476-5381.1984.tb16524.x

    authors: Einstein R,Lavidis NA

    更新日期:1984-12-01 00:00:00

  • Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells.

    abstract::Mast cells participate in allergies, and also in immunity and inflammation by secreting proinflammatory cytokines. Flavonoids are naturally occurring polyphenolic plant compounds, one group of which -- the flavonols, inhibits histamine and some cytokine release from rodent basophils and mast cells. However, the effect...

    journal_title:British journal of pharmacology

    pub_type: 杂志文章

    doi:10.1038/sj.bjp.0706246

    authors: Kempuraj D,Madhappan B,Christodoulou S,Boucher W,Cao J,Papadopoulou N,Cetrulo CL,Theoharides TC

    更新日期:2005-08-01 00:00:00