Abstract：
:Summary 1. The non-selective K(+) channel blocker 4-aminopyridine (4-AP) has shown clinical efficacy in the treatment of neurological disorders such as multiple sclerosis. The clinical usefulness of 4-AP is hampered by its ability to produce seizures. Nerispirdine, an analogue of 4-AP, is currently under clinical investigation for the treatment of multiple sclerosis. In contrast with 4-AP, nerispirdine is not proconvulsant, suggesting mechanistic differences between the two drugs. 2. Using whole-cell patch-clamp electrophysiology, we compared the effects of 4-AP and nerispirdine on the cloned human K(+) channels K(v)1.1 and K(v)1.2, expressed in Chinese hamster ovary cells, and on voltage-dependent Na(+) channels recorded from human SH-SY5Y cells. 3. Nerispirdine inhibited K(v)1.1 and K(v)1.2 with IC(50) values of 3.6 and 3.7 micromol/L, respectively. 4-Aminopyridine was approximately 50-fold less potent at blocking these channels. Nerispirdine also inhibited voltage-dependent Na(+) channel currents recorded from human SH-SY5Y cells with an IC(50) of 11.9 micromol/L when measured from a -70 mV holding potential. In contrast, 4-AP had no effect on Na(+) channel currents. 4. The results demonstrate that nerispirdine, like 4-AP, can inhibit axonal K(+) channels and that this mechanism may underlie the ability of the drug to enhance neuronal conduction. Unlike 4-AP, nerispirdine can also inhibit neuronal Na(+) channels, a mechanism that may explain why nerispirdine lacks proconvulsant activity.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Smith C,Kongsamut S,Wang H,Ji J,Kang J,Rampe Ddoi
10.1111/j.1440-1681.2009.05200.xsubject
Has Abstractpub_date
2009-11-01 00:00:00pages
1104-9issue
11eissn
0305-1870issn
1440-1681pii
CEP5200journal_volume
36pub_type
杂志文章abstract：:There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to inves...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12395
更新日期：2015-06-01 00:00:00
abstract：:1. To investigate the pharmacological effects of T-1095, this novel derivative of phlorizin was administered to GK rats for 8 weeks. T-1095 treatment significantly lowered plasma glucose and glycosylated haemoglobin (HbA1c) levels, but did not significantly affect bodyweight. 2. T-1095 treatment did not affect 3.3 mmo...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2002.03671.x
更新日期：2002-05-01 00:00:00
abstract：:Asymmetric dimethylarginine (ADMA) is an endogenously produced nitric oxide synthase (NOS) inhibitor. L-Arginine can be metabolised by NOS and arginase, and arginase is the first step in polyamine production necessary for cellular proliferation. We tested the hypothesis that ADMA would inhibit NOS but not arginase act...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12252
更新日期：2014-07-01 00:00:00
abstract：:1. The effect of enalapril on handling of an Na load and on body Na during 96 h of zero Na intake was measured in hypertensive rats (GH and SHR) and their normotensive controls (N and WKY) by a whole body counting method. 2. Enalapril treatment led to a greater fall in body Na in the first 24 h after the Na load (as e...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1992.tb00475.x
更新日期：1992-05-01 00:00:00
abstract：:1. The aim of the present study was to examine the effect of bacterial lipopolysaccharide (LPS) on the disposition of an organic anion transporting polypeptide and P-glycoprotein substrate in the rat isolated perfused liver. 2. Male Sprague-Dawley rats were divided into four groups. Three of the groups received 1, 2.5...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2006.04419.x
更新日期：2006-08-01 00:00:00
abstract：:1. Blood pressure (BP) and heart rate (HR) increase 6 and 24 h after sinoaortic baroreceptor denervation (SAD), whereas plasma renin activity (PRA) and renal renin mRNA levels remain unchanged. We postulated that a simultaneous rise in BP could offset the expected activation of renin associated with an increased renal...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2006.04389.x
更新日期：2006-05-01 00:00:00
abstract：:1. Altered calcium regulation has been observed in experimental and human hypertension. In this study erythrocyte (RBC) intracellular calcium concentration ([Ca2+]i) was compared in conscious spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) at rest and after injection of the dihydropyridine ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1988.tb01068.x
更新日期：1988-04-01 00:00:00
abstract：:This study explored the effects and mechanisms of dopamine D1 receptors (DR1) activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF-38393 decreased the viability of OS732 cells and increased their rate of apoptosis, whereas the DR1 antagonist SCH-23390 abolished the effects of SKF-38393. In OS7...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 信件
doi：10.1111/1440-1681.12814
更新日期：2017-11-01 00:00:00
abstract：:1. Whole-cell patch recordings were made from antidromically identified sympathetic preganglionic neurons (SPN) of immature rat spinal cord slices. Bath application of nociceptin (0.1-1 micromol/L) suppressed excitatory postsynaptic potentials (EPSP) and hyperpolarized a population of SPN; these effects were naloxone ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2002.03635.x
更新日期：2002-03-01 00:00:00
abstract：:Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery. A steady-state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excre...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1985.tb02311.x
更新日期：1985-03-01 00:00:00
abstract：:1. The role of cardiac reflexes in baroreflex control mechanisms and the changes that occur in chronic hypertension is reviewed. The rapid resetting properties of the arterial baroreceptors ensures its role in short-term rather than long-term control of blood pressure. 2. In hypertensive humans and animals, the barore...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.1994.tb02448.x
更新日期：1994-10-01 00:00:00
abstract：:1. Effects of a newly developed phosphodiesterase (PDE) III inhibitor, E-1020, on intracellular calcium transients were compared with those of isoproterenol (ISO) in isolated single myocytes from failing hearts secondary to pulmonary hypertension induced by monocrotaline injection. Myocytes were isolated by enzyme dig...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1994.tb02663.x
更新日期：1994-12-01 00:00:00
abstract：:1. Clinical pharmacology requires numerous skills and most activities involve interactions with other specialities, both clinical and experimental. 2. A range of experts has had a major influence on the nature and design of my research, which is illustrated by the evolution of my knowledge of adverse drug reactions an...
journal_title：Clinical and experimental pharmacology & physiology
pub_type：
doi：10.1046/j.1440-1681.2001.03542.x
更新日期：2001-11-01 00:00:00
abstract：:The present study aimed to investigate the relationship between normal serum concentrations of thyrotropin (TSH) and urinary incontinence (IU), urinary infections, and quality of life in old women. Euthyroid post-menopausal women without sarcopenia, estrogen replacement, emotional illness, and/or cancer were enrolled ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12788
更新日期：2017-12-01 00:00:00
abstract：:1. The present study compared the binding and functional characteristics of tachykinin NK2 receptors in human detrusor muscle with those in human colon circular muscle. 2. In radioligand binding studies, similar KD values were observed for tachykinin NK2 receptor radioligands [125I]-neurokinin (NK) A, [125I]-[Lys5,Tyr...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2003.03887.x
更新日期：2003-09-01 00:00:00
abstract：:1. NBPA is a derivative of 3-n-butylpathalide isolated from Apium granolens Linn. 2. At concentrations ranging from 6 x 10(-6) to 10(-6) mol/L, NBPA inhibited the L-type calcium current in guinea-pig myocardial cells and cultured human neuroblastoma cells. 3. At 10(-6) mol/L, NBPA markedly inhibited calcium-dependent ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.1999.03144.x
更新日期：1999-10-01 00:00:00
abstract：:1. Renomedullary interstitial cells (RMIC), abundant throughout the medulla of the kidney, have been demonstrated to have binding sites for many vasoactive peptides, including atrial natriuretic peptide, endothelin, angiotensin II and bradykinin (BK). These observations would support the hypothesis that interactions b...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.1999.02981.x
更新日期：1999-01-01 00:00:00
abstract：:Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that develops as a consequence of prolonged hyperglycaemia-induced injury to the long nerves. Apart from pain, PDN is also characterized by morphine hyposensitivity. Intriguingly, in streptozotocin (STZ)-induced diabetic rats exhibiting marked ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.13091
更新日期：2019-07-01 00:00:00
abstract：:1. Using a nested case-control study of 661 non-institutionalized elderly (> or = 60 years) residents of Dubbo, New South Wales, Australia, the aim of this study is to determine whether the A1166C polymorphism of the angiotensin II type I (AT1) receptor gene is associated with hypertension in the elderly. 2. Individua...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.1999.03066.x
更新日期：1999-07-01 00:00:00
abstract：:Members of the transient receptor potential (TRP) channel superfamily are present in vascular smooth muscle cells and play important roles in the regulation of vascular contractility. The TRPC3 and TRPC6 channels are activated by stimulation of several excitatory receptors in vascular smooth muscle cells. Activation o...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2007.04855.x
更新日期：2008-09-01 00:00:00
abstract：:1. Rats fed high dietary fructose are documented to form an acquired model of insulin resistance. The present study measured the effects of administration of L-carnitine (CA) on lens protein glycation, oxidative stress and redox homeostasis in rats fed a high-fructose diet. 2. Animals were divided into four groups: (i...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2007.04815.x
更新日期：2008-02-01 00:00:00
abstract：:1. Hepatic resection with concomitant periods of ischaemia and reperfusion (I/R) is required to perform reduced-size liver (RSL) transplantation procedures, such as living donor or split liver transplantation. Although a great deal of progress has been made using these types of surgical procedures, a significant numbe...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2007.04640.x
更新日期：2007-09-01 00:00:00
abstract：:1. In the rectum and distal nephron, sodium reabsorption is mediated by the amiloride-sensitive epithelial sodium channel (ENaC). The ENaC-mediated sodium transport is electrogenic and creates an amiloride-sensitive transepithelial potential difference (PD). 2. We have evaluated the salt- and angiotensin (Ang)II-depen...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2000.03204.x
更新日期：2000-01-01 00:00:00
abstract：:1. Plasma concentrations of prorenin were determined in a transgenic animal model of nephropathy induced by overexpression of transforming growth factor (TGF)-beta1 in the juxtaglomerular apparatus. 2. In both female and male mice, plasma concentrations of prorenin were higher in transgenic than in non-transgenic anim...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2000.03330.x
更新日期：2000-09-01 00:00:00
abstract：:1. Taurine and homocysteine are metabolites of methionine. Hyperhomocysteinaemia is one of the risk factors for cardiovascular disease. Although taurine may be a cardiovascular cytoprotective substance, we hypothesized that it may antagonize the effects of homocysteine on myocardial mitochondrial function. 2. We studi...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2004.03983.x
更新日期：2004-04-01 00:00:00
abstract：:1. Insulin-like growth factor (IGF)-I has acute effects on cardiovascular function, including a well-characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF-I also has effects on a variety of other signalling pathways that affect vascular tone, in particular ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2006.04510.x
更新日期：2006-12-01 00:00:00
abstract：:Direct evidence is limited for the association between heart rate variability (HRV) indices and ventricular tachyarrhythmias (VTAs). While galectin-3 (Gal-3) is regarded as a causal factor for cardiac remodelling and a biomarker for arrhythmias, its regulation on VTAs and HVR is unknown. Using aged transgenic (TG) mic...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.13275
更新日期：2020-07-01 00:00:00
abstract：:1. The leucocyte-mediated inflammatory response plays a pivotal role in ischaemia-reperfusion injury. P-Selectin and CD11b are important mediators for the recruitment of leucocytes into the endothelium. However, the time-course of changes in P-selectin and CD11b expression during reperfusion is not defined. Magnesium ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2007.04697.x
更新日期：2007-12-01 00:00:00
abstract：:Transthyretin (TTR) is a binding protein for the thyroid hormone thyroxine (T4 ), retinol and β-amyloid peptide. TTR aids the transfer of T4 from the blood to the cerebrospinal fluid (CSF), but also prevents T4 loss from the blood-CSF barrier. It is, however, unclear whether TTR affects the clearance of β-amyloid from...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12598
更新日期：2016-09-01 00:00:00
abstract：:1. The effect of propofol on cardiac whole-cell sodium currents and single sodium channels in rat isolated ventricular myocytes was examined using patch-clamp techniques. 2. Propofol caused a block of the whole-cell sodium current, the potency of block depending on the holding potential. When cells were held at -90 mV...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1998.tb02360.x
更新日期：1998-05-01 00:00:00
