bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of thymol on calcium and potassium currents in canine and human ventricular cardiomyocytes
Authors: Magyar János , Szentandrássy Norbert , Bányász Tamás , Fülöp László , Varró András , Nánási Péter P 
Published: January 2005

Concentration‐dependent effects of thymol (1–1000 μM) was studied on action potential configuration and ionic currents in isolated canine ventricular cardiomyocytes using conventional microelectrode and patch clamp techniques.
Low concentration of thymol (10 μM) removed the notch of the action potential, whereas high concentrations (100 μM or higher) caused an additional shortening of action potential duration accompanied by progressive depression of plateau and reduction of Vmax.
In the canine cells L‐type Ca current (ICa) was decreased by thymol in a concentration‐dependent manner (EC50: 158±7 μM, Hill coeff.: 2.96±0.43). In addition, thymol (50–250 μM) accelerated the inactivation of ICa, increased the time constant of recovery from inactivation, shifted the steady‐state inactivation curve of ICa leftwards, but voltage dependence of activation remained unaltered. Qualitatively similar results were obtained with thymol in ventricular myocytes isolated from healthy human hearts.
Thymol displayed concentration‐dependent suppressive effects on potassium currents: the transient outward current, Ito (EC50: 60.6±11.4 μM, Hill coeff.: 1.03±0.11), the rapid component of the delayed rectifier, IKr (EC50: 63.4±6.1 μM, Hill coeff.: 1.29±0.15), and the slow component of the delayed rectifier, IKs (EC50: 202±11 μM, Hill coeff.: 0.72±0.14), however, K channel kinetics were not much altered by thymol. These effects on Ca and K currents developed rapidly (within 0.5 min) and were readily reversible.
In conclusion, thymol suppressed cardiac ionic channels in a concentration‐dependent manner, however, both drug‐sensitivities as well as the mechanism of action seems to be different when blocking calcium and potassium channels.

British Journal of Pharmacology (2002) 136, 330–338; doi:10.1038/sj.bjp.0704718
Beneficial effects of caffeic acid phenethyl ester in a rat model of vascular injury
Authors: Maffia Pasquale , Ianaro Angela , Pisano Barbara , Borrelli Francesca , Capasso Francesco , Pinto Aldo , Ialenti Armando 
Published: January 2005

The aim of this study was to evaluate whether caffeic acid phenethyl ester (CAPE), an active component of propolis, was able to reduce neointimal formation in a model of endothelial injury of rat carotid artery (balloon angioplasty). Furthermore, we investigated the relationship between neointima formation and nuclear factor‐κB (NF‐κB) activation and we correlated NF‐κB activation to the expression of inducible isoform of cyclo‐oxygenase (COX‐2) in injured carotids.
In control group a significant proliferation of neointima was observed 14 days after balloon angioplasty, which was correlated to an increase of NF‐κB/DNA binding activity as well as p50/p65 nuclear levels compared to those observed in the carotids from sham‐operated rats. Furthermore, NF‐κB activation was correlated to increased COX‐2, but not β‐actin, protein expression.
Treatment of rats for 14 days with CAPE (3, 10, 30 mg kg−1) caused a significant inhibition of all the parameters assayed, except β‐actin protein expression.
These results indicate that treatment with CAPE may lead to a reduction of neointima formation by inhibiting NF‐κB activation and suggest that this agent may have therapeutic relevance for the prevention of human restenosis.

British Journal of Pharmacology (2002) 136, 353–360; doi:10.1038/sj.bjp.0704720
E3040 sulphate, a novel thromboxane synthase inhibitor, blocks the Cl− secretion induced by platelet‐activating factor in isolated rat colon
Authors: Sakai Hideki , Suzuki Tomoyuki , Murota Miki , Oketani Kiyoshi , Uchiumi Takaoki , Murakami Manabu , Takeguchi Noriaki 
Published: January 2005

E3040 (6‐hydroxy‐5,7‐dimethyl‐2‐methylamino‐4‐(3‐pyridylmethyl)benzothiazole), is a novel dual inhibitor of 5‐lipoxygenase (5‐LOX) and thromboxane synthase (Tx synthase). Here, we examined the effects of E3040 sulphate, a sulphate conjugate of E3040, on these enzyme activities in cell‐free systems and on the thromboxane A2 (TxA2)‐mediated Cl− secretion induced by platelet‐activating factor (PAF) in isolated rat colons.
E3040 sulphate inhibited Tx synthase activity in a concentration‐dependent manner (IC50=0.013 μM), whereas it induced little effects on 5‐LOX and cyclo‐oxygenase activities (IC50>100 μM) with the cell‐free enzyme assay.
With isolated rat colonic mucosa, E3040 sulphate in a concentration‐dependent manner (IC50=1.8 μM) inhibited the Cl− secretion induced by 10 μM PAF. On the other hand, E3040 sulphate (30 μM) induced no effect on the prostaglandin E2 (0.5 μM)‐ and leukotriene D4 (1 μM)‐induced Cl− secretion in the colon.
PAF (10 μM) increased a release of TxB2, a stable metabolite of TxA2, from the colonic mucosa. This increase was significantly inhibited by subsequent addition of E3040 sulphate (30 μM).
Probenecid (100 μM), an inhibitor of organic anion transporter, abolished the inhibitory effect of E3040 sulphate on the PAF‐induced Cl− secretion. Another inhibitor, sulphobromophthalein (30 μM) partially but significantly attenuated the effect of E3040 sulphate. p‐Aminohippuric acid (1 mM) had no effect.
These findings suggest that E3040 sulphate is a novel Tx synthase inhibitor, and that E3040 sulphate taken up into the colonic cells by organic anion transporters inhibits the PAF‐induced Cl− secretion by blocking a release of TxA2.

British Journal of Pharmacology (2002) 136, 383–390; doi:10.1038/sj.bjp.0704723
Increased arginase activity underlies allergen‐induced deficiency of cNOS‐derived nitric oxide and airway hyperresponsiveness
Authors: Meurs Herman , McKay Sue , Maarsingh Harm , Hamer Marco A M , Macic Lejla , Molendijk Niek , Zaagsma Johan 
Published: January 2005

A deficiency of constitutive nitric oxide synthase (cNOS)‐derived nitric oxide (NO), due to reduced availability of L‐arginine, importantly contributes to allergen‐induced airway hyperresponsiveness (AHR) after the early asthmatic reaction (EAR). Since cNOS and arginase use L‐arginine as a common substrate, we hypothesized that increased arginase activity is involved in the allergen‐induced NO deficiency and AHR.
Using a guinea‐pig model of allergic asthma, we addressed this hypothesis by examining the effects of the specific arginase inhibitor Nω‐hydroxy‐nor‐L‐arginine (nor‐NOHA) on the responsiveness to methacholine of isolated perfused tracheae from unchallenged control animals and from animals 6 h after ovalbumin challenge. Arginase activity in these preparations was investigated by measuring the conversion of L‐[14C]arginine to [14C]urea.
Airways from allergen‐challenged animals showed a 2 fold (P<0.001) increase in responsiveness to intraluminal (IL) administration of methacholine compared to controls. A similar hyperresponsiveness (1.8 fold, P<0.01) was observed in control airways incubated with the NOS inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME, 0.1 mM, IL), while L‐NAME had no further effect on the airways from challenged animals.
Remarkably, 5 μM nor‐NOHA (IL) normalized the hyperresponsiveness of challenged airways to basal control (P<0.001), and this effect was fully reversed again by 0.1 mM L‐NAME (P<0.05). Moreover, arginase activity in homogenates of the hyperresponsive airways was 3.5 fold (P<0.001) enhanced compared to controls.
The results indicate that enhanced arginase activity contributes to allergen‐induced deficiency of cNOS‐derived NO and AHR after the EAR, presumably by competition with cNOS for the common substrate, L‐arginine. This is the first demonstration that arginase is involved in the pathophysiology of asthma.

British Journal of Pharmacology (2002) 136, 391–398; doi:10.1038/sj.bjp.0704725
AT2 receptor‐dependent vasodilation is mediated by activation of vascular kinin generation under flow conditions
Authors: Katada Jun , Majima Masataka 
Published: January 2005

Physiological roles of angiotensin II type 2 receptor (AT2) are not well defined. This study was designed to investigate the mechanisms of AT2‐dependent vascular relaxation by studying vasodilation in pressurized and perfused rat mesenteric arterial segments.
Perfusion of angiotensin II in the presence of AT1 antagonist elicited vascular relaxation, which was completely dependent on AT2 receptors on endothelium. FR173657 (>1 μM), a bradykinin (BK) B2‐specific antagonist, significantly suppressed AT2‐dependent vasodilation (maximum inhibition: 68.5% at 10 μM).
Kininogen‐deficient Brown Norway Katholiek rats showed a significant reduction in AT2‐mediated vasodilatory response compared with normal wild‐type Brown Norway rats.
Indomethacin (>1 μM), aprotinin (10 μM) and soybean trypsin inhibitor (10 μM) also reduced AT2‐dependent vasodilation.
Our results demonstrated that stimulation of AT2 receptors caused a significant vasodilation through local production of BK in resistant arteries of rat mesentery in a flow‐dependent manner. Such vasodilation counterbalances AT1‐dependent vasoconstriction to regulate the vascular tone.

British Journal of Pharmacology (2002) 136, 484–491; doi:10.1038/sj.bjp.0704731
An investigation of the effects of zaprinast, a PDE inhibitor, on the nitrergic control of the urethra in anaesthetized female rats
Authors: Wibberley Alexandra , Nunn Philip A , Naylor Alasdair M , Ramage Andrew G 
Published: January 2005

The effects of L‐NAME and zaprinast were investigated (i.v.) on reflex‐evoked changes in bladder and urethral pressures in urethane‐anaesthetized female rats.
L‐NAME attenuated reflex‐evoked urethral relaxations (65±10%), while zaprinast potentiated these responses (68±24%). L‐NAME and zaprinast also increased baseline urethral pressure and urethral striated muscle (EUS‐EMG) activity. These drugs had little effect on the bladder.
Following pre‐treatment with α‐bungarotoxin (i.v.) to block urethral striated muscle, L‐NAME and zaprinast failed to increase baseline urethral pressure. Further zaprinast failed to alter the size of reflex‐evoked urethral relaxations.
Intra‐urethral zaprinast caused a significant increase while sodium nitroprusside (SNP) and isoprenaline caused decreases in urethral pressure (+14±3%, −25±5%, −29±7%, respectively). These changes were associated with increases in EUS‐EMG activity. After chlorisondamine (i.v.), zaprinast caused a significant fall in urethral pressure, while the decrease in urethral pressure caused by SNP and isoprenaline was potentiated. No changes in EUS‐EMG activity occurred.
These results indicate that a nitrergic pathway mediates reflex‐evoked urethral smooth muscle relaxations. The data also indicates that there is a background release of NO, which reduces sphincter skeletal muscle activity. Further, the ability of zaprinast to potentiate nitrergic evoked urethral relaxations involves an increase in striated muscle tone. This appears to be an indirect result of smooth muscle relaxation and is mediated, at least in part, by a chlorisondamine‐sensitive mechanism.

British Journal of Pharmacology (2002) 136, 399–414; doi:10.1038/sj.bjp.0704735
Central injections of nocistatin or its C‐terminal hexapeptide exert anxiogenic‐like effect on behaviour of mice in the plus‐maze test
Authors: Gavioli Elaine C , Rae Giles A , Calo' Girolamo , Guerrini Remo , De Lima Thereza C M 
Published: January 2005

Nocistatin (NST) antagonizes several actions of nociceptin/orphanin FQ (N/OFQ), but acts on distinct receptors. As N/OFQ exerts anxiolytic‐like actions in various tests, its behavioural actions in the elevated plus‐maze (EPM) test were compared with those of bovine NST.
Five minutes after i.c.v. treatment, mice were placed on the EPM for 5 min and entries into and time spent on open and closed arms were recorded alongside other parameters.
NST (0.1 – 3 pmol) reduced percentages of entries into (control 39.6±3.1%, peak effect at 1 pmol NST 8.5±2.9%) and time spent on open arms (control 30.8±2.3%, NST 2.7±1.5%). The C‐terminal hexapeptide of NST (NST‐C6; 0.01 – 10 pmol) closely mimicked these actions of NST, with peak effects at 0.1 pmol.
N/OFQ (1 – 100 pmol) increased percentages of entries into (control 38.5±3.4%; peak effect at 10 pmol N/OFQ 67.9±4.9%) and time spent on open arms (control 32.0±3.8%; N/OFQ 74.9±5.8%). Closed arm entries, an index of locomotor activity, were unchanged by all peptides.
Effects of NST or NST‐C6, but not N/OFQ, were still detectable 15 min after injection. Behaviour of animals co‐injected with NST (1 pmol) or NST‐C6 (0.1 pmol) plus N/OFQ (10 pmol) was indistinguishable from that of controls.
These results reveal potent anxiogenic‐like actions of NST and NST‐C6, and confirm the anxiolytic‐like properties of N/OFQ. As NST and N/OFQ both derive from preproN/OF, anxiety may be modulated in opposing directions depending on how this precursor is processed.

British Journal of Pharmacology (2002) 136, 764–772; doi:10.1038/sj.bjp.0704739
Effects of nitric oxide donors on cardiac contractility in wild‐type and myoglobin‐deficient mice
Authors: Wegener J W , Gödecke A , Schrader J , Nawrath H 
Published: January 2005

The effects of the nitric oxide (NO) donors S‐nitroso‐N‐acetylpenicillamine (SNAP), sodium(Z)‐1‐(N,N‐diethylamino)diazen‐1‐ium‐1,2‐diolate (DEA‐NONOate), and (Z)‐1‐[N‐(2‐Aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA‐NONOate) on force of contraction (Fc) were studied in atrial and ventricular muscle strips obtained from wild‐type (WT) and myoglobin‐deficient (myo−/−) mice.
SNAP slightly reduced Fc in preparations from WT mice at concentrations above 100 μM; this effect was more pronounced in myo−/− mice.
DEA‐NONOate reduced Fc in preparations from myo−/− mice to a larger extent than those from WT mice.
DETA‐NONOate reduced Fc in preparations from myo−/− but not from WT mice.
Pre‐incubation with an inhibitor of the soluble guanylyl cyclase (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one; 100 μM) prevented the effects of SNAP, DEA‐NONOate and DETA‐NONOate on Fc in myo−/− mice.
It is suggested that, in physiological conditions, myoglobin acts as intracellular scavenger preventing NO from reaching its intracellular receptors in cardiomyocytes, whereas, in myoglobin‐deficient conditions, NO is able to reduce contractility via activation of the soluble guanylyl cyclase/cyclic GMP pathway.

British Journal of Pharmacology (2002) 136, 415–420; doi:10.1038/sj.bjp.0704740
Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells
Authors: Fujino Takayuki , Yuhki Koh‐ichi , Yamada Takehiro , Hara Akiyoshi , Takahata Osamu , Okada Yuji , Xiao Chun‐Yang , Ma Hong , Karibe Hideji , Iwashima Yasunori , Fukuzawa Jun , Hasebe Naoyuki , Kikuchi Kenjiro , Narumiya Shuh , Ushikubi Fumitaka 
Published: January 2005

Effects of the prostanoids on the growth of cultured aortic vascular smooth muscle cells (VSMCs) were examined using mice lacking prostanoid receptors.
Proliferation of VSMCs was assessed by measuring [3H]‐thymidine incorporation and the cell number, and their hypertrophy by [14C]‐leucine incorporation and protein content.
In VSMCs from wild‐type mice, expressions of mRNAs for the EP4 and TP were most abundant, followed by those for the IP, EP3 and FP, when examined by competitive reverse transcriptase‐PCR. Those for the EP1, EP2 and DP, however, could not be detected.
AE1‐329, an EP4 agonist, and cicaprost, an IP agonist, inhibited platelet derived growth factor (PDGF)‐induced proliferation of VSMCs from wild‐type mice; these inhibitory effects disappeared completely in VSMCs from EP4−/− and IP−/− mice, respectively. In accordance with these effects, AE1‐329 and cicaprost stimulated cAMP production in VSMCs from wild‐type mice, which were absent in VSMCs from EP4−/− and IP−/− mice, respectively.
Effects of PGE2 on cell proliferation and adenylate cyclase were almost similar with those of AE1‐329 in VSMCs from wild‐type mice, which disappeared in VSMCs from EP4−/− mice.
PGD2 inhibited PDGF‐induced proliferation of VSMCs from both wild‐type and DP−/− mice to a similar extent. This action of PGD2 was also observed in VSMCs from EP4−/− and IP−/− mice.
In VSMCs from wild‐type mice, I‐BOP, a TP agonist, showed potentiation of PDGF‐induced hypertrophy. I‐BOP failed to show this action in VSMCs from TP−/− mice.
The specific agonists for the EP1, EP2 or EP3, and PGF2α showed little effect on the growth of VSMCs.
These results show that PGE2, PGI2 and TXA2 modulate PDGF‐induced proliferation or hypertrophy of VSMCs via the EP4, IP and TP, respectively, and that the inhibitory effect of PGD2 on PDGF‐induced proliferation is not mediated by the DP, EP4 or IP.

British Journal of Pharmacology (2002) 136, 530–539; doi:10.1038/sj.bjp.0704749
Influence of the CB1 receptor antagonist, AM 251, on the regional haemodynamic effects of WIN‐55212‐2 or HU 210 in conscious rats
Authors: Gardiner S M , March J E , Kemp P A , Bennett T 
Published: January 2005

In conscious, freely‐moving, male, Sprague‐Dawley rats, the regional haemodynamic responses to the synthetic cannabinoids, WIN‐55212‐2 and HU 210, were compared. The possible involvement of cannabinoid, CB1‐receptors, or β2‐adrenoceptors in the responses to WIN‐55212‐2 and HU 210 were investigated using the CB1‐receptor antagonist, AM 251, or the β2‐adrenoceptor antagonist, ICI 118551, respectively.
Both WIN‐55212‐2 (150 μg kg−1) and HU 210 (100 μg kg−1) had pressor, renal, and mesenteric vasoconstrictor and hindquarters vasodilator actions, although the effects of HU 210 were much more sustained than those of WIN‐55212‐2. Lower doses of the cannabinoids (WIN‐55212‐2, 50 μg kg−1, HU 210, 10 μg kg−1) had less consistent actions.
All the significant cardiovascular effects of WIN‐55212‐2 and HU 210 were antagonized by pretreatment with AM 251 (3 mg kg−1). Furthermore, pretreatment with the β2‐adrenoceptor antagonist, ICI 118551, inhibited the hindquarters vasodilator effects of WIN‐55212‐2 and of HU 210.
On the basis of the present findings, and our earlier work, it is suggested that, in conscious rats, the pressor and vasoconstrictor effects of HU 210 and WIN‐55212‐2 involve cannabinoid‐receptor‐mediated increases in sympathetic activity. The accompanying hindquarters vasodilator actions of these agonists are cannabinoid receptor‐mediated and appear to involve β2‐adrenoceptors.

British Journal of Pharmacology (2002) 136, 581–587; doi:10.1038/sj.bjp.0704750
Blockade of neuropeptide Y2 receptors and suppression of NPY's anti‐epileptic actions in the rat hippocampal slice by BIIE0246
Authors: Bahh Bouchaïb El , Cao Jeffrey Q , Beck‐Sickinger Annette G , Colmers William F 
Published: January 2005

Neuropeptide Y (NPY) has been shown to suppress synaptic excitation in rat hippocampus by a presynaptic action. The Y2 (Y2R) and the Y5 (Y5R) receptors have both been implicated in this action. We used the non‐peptide, Y2R‐selective antagonist, BIIE0246, to test the hypothesis that the Y2R mediates both the presynaptic inhibitory and anti‐epileptic actions of NPY in rat hippocampus in vitro.
NPY and the Y2R‐selective agonist, [ahx5‐24]NPY, both inhibited the population excitatory postsynaptic potential (pEPSP) evoked in area CA1 by stratum radiatum stimulation in a concentration‐dependent manner. BIIE0246 suppressed the inhibitory effects of both agonists, suppressing the maximal inhibition without causing a change in the agonist EC50, in a manner inconsistent with competitive antagonism.
BIIE0246 washed out from hippocampal slices extremely slowly. Application of agonist at high concentrations (1–3 μM) for prolonged periods did not alter the rate of washout, but did partially overcome the antagonism, inconsistent with an insurmountable antagonism by BIIE0246.
In the stimulus train‐induced bursting (STIB) model of ictal activity in hippocampal slices, both NPY and [ahx5‐24]NPY inhibited primary afterdischarge (1°AD) activity. BIIE0246 (100 nM) completely suppressed the actions of NPY and [ahx5‐24]NPY in this model. In contrast, the potent Y5R‐selective agonist, Ala31Aib32NPY, affected neither 1°AD activity in the presence of BIIE0246, nor, by itself, even the pEPSP in CA1.
BIIE0246 potently suppresses NPY actions in rat hippocampus, suggesting a dominant role for Y2R there. The apparently insurmountable antagonism observed may result from the lipophilic nature of the antagonist.

British Journal of Pharmacology (2002) 136, 502–509; doi:10.1038/sj.bjp.0704751
Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide‐ and kinin‐dependent mechanism
Authors: Xu Biao , Xiao‐hong Li , Lin Gao , Queen Lindsay , Ferro Albert 
Published: January 2005

We investigated the nitric oxide (NO) dependence of vasorelaxation in response to different calcium channel blockers (CCB), in rabbit femoral artery in vivo.
Anaesthetized rabbits underwent femoral artery ligation, and blood from the proximal artery was returned distal to the ligature through a constant infusion pump. The effects of local injection of CCB on perfusion pressure and plasma nitrite+nitrate (NOx, which reflects local NO biosynthesis) concentration in this system were determined.
Intra‐arterial verapamil, nifedipine or amlodipine 10 μmol kg−1 each reduced perfusion pressure. Pre‐treatment with intra‐arterial NG‐nitro‐L‐arginine methyl ester (L‐NAME, a NO synthase inhibitor) 1 μmol kg−1 did not affect responses to verapamil or nifedipine, but attenuated the reduction in perfusion pressure to amlodipine, from 33.2±2.1% to 22.5±1.6% (P=0.002).
Intra‐arterial amlodipine  –  unlike verapamil or nifedipine  –  increased femoral venous NOx, from 9.1±0.4 μM to 14.1±0.5 μM (P=0.005).
The bradykinin B2 receptor antagonist HOE 140, 30 mg kg−1, attenuated the reduction in perfusion pressure and abolished the rise in venous NOx concentration, following intra‐arterial amlodipine.
Amlodipine potently inhibited serum angiotensin converting‐enzyme (ACE) activity in vitro, as effectively as enalapril at similar concentrations.
These results suggest that the vasorelaxant effects of nifedipine and verapamil are NO‐independent, whereas those of amlodipine are partly NO‐dependent, in rabbit femoral artery in vivo. This effect of amlodipine occurs through B2 receptor activation, and may be related to an increase in local bradykinin through inhibition of ACE.

British Journal of Pharmacology (2002) 136, 375–382; doi:10.1038/sj.bjp.0704753
Enhancement of delayed‐rectifier potassium conductance by low concentrations of local anaesthetics in spinal sensory neurones
Authors: Olschewski Andrea , Wolff Matthias , Bräu Michael E , Hempelmann Gunter , Vogel Werner , Safronov Boris V 
Published: January 2005

Combining the patch‐clamp recordings in slice preparation with the ‘entire soma isolation’ method we studied action of several local anaesthetics on delayed‐rectifier K+ currents in spinal dorsal horn neurones.
Bupivacaine, lidocaine and mepivacaine at low concentrations (1–100 μM) enhanced delayed‐rectifier K+ current in intact neurones within the spinal cord slice, while exhibiting a partial blocking effect at higher concentrations (>100 μM). In isolated somata 0.1–10 μM bupivacaine enhanced delayed‐rectifier K+ current by shifting its steady‐state activation characteristic and the voltage‐dependence of the activation time constant to more negative potentials by 10–20 mV.
Detailed analysis has revealed that bupivacaine also increased the maximum delayed‐rectifier K+ conductance by changing the open probability, rather than the unitary conductance, of the channel.
It is concluded that local anaesthetics show a dual effect on delayed‐rectifier K+ currents by potentiating them at low concentrations and partially suppressing at high concentrations. The phenomenon observed demonstrated the complex action of local anaesthetics during spinal and epidural anaesthesia, which is not restricted to a suppression of Na+ conductance only.

British Journal of Pharmacology (2002) 136, 540–549; doi:10.1038/sj.bjp.0704754