bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide, prostanoid and non‐NO, non‐prostanoid involvement in acetylcholine relaxation of isolated human small arteries
Authors: Buus Niels H , Simonsen Ulf , Pilegaard Hans K , Mulvany Michael J 
Published: January 2005

The main purpose of the study was to clarify to which extent nitric oxide (NO) contributes to acetylcholine (ACh) induced relaxation of human subcutaneous small arteries.
Arterial segments were mounted in myographs for recording of isometric tension, NO concentration and smooth muscle membrane potential.
In noradrenaline‐contracted arteries, ACh induced endothelium‐dependent relaxations. The NO synthase inhibitor, NG‐nitro‐L‐arginine (L‐NOARG) had a small significant effect on the concentration‐response curves for ACh, and in the presence of L‐NOARG, indomethacin only caused a small additional rightward shift in the ACh relaxation.
The NO scavenger, oxyhaemoglobin attenuated relaxations for ACh and for the NO donor S‐nitroso‐N‐acetylpenicillamine (SNAP). Inhibition of guanylyl cyclase with 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxaline‐1‐one (ODQ), and inhibition of protein kinase G with β‐phenyl‐1, N2‐etheno‐8‐bromoguanosine‐ 3′, 5′‐ cyclic monophosphorothioate, Rp‐isomer, slightly attenuated ACh relaxation, but abolished SNAP induced relaxation.
ACh induced relaxation without increases in the free NO concentration. In contrast, for equivalent relaxation, SNAP increased the NO concentration 32±8 nM.
ACh hyperpolarized the arterial smooth muscle cells with 11.4±1.3 mV and 10.5±1.3 mV in the absence and presence of L‐NOARG, respectively. SNAP only elicited a hyperpolarization of 1.6±0.9 mV.
In the presence of indomethacin and L‐NOARG, ACh relaxation was almost unaffected by lipoxygenase inhibition with nordihydroguaiaretic acid, or cytochrome P450 inhibition with 17‐octadecynoic acid or econazole. ACh relaxation was strongly reduced by the combination of charybdotoxin and apamin, but small increments in the extracellular potassium concentration induced no relaxations.
The study demonstrates that the NO/L‐arginine pathway is present in human subcutaneous small arteries and to a limited extent is involved in ACh induced relaxation. The study also suggests a small contribution of arachidonic acid metabolites. However, ACh relaxation is mainly dependent on a non‐NO, non‐prostanoid endothelium dependent hyperpolarization.

British Journal of Pharmacology (2000) 129, 184–192; doi:10.1038/sj.bjp.0703041
The metabolism of clomethiazole in gerbils and the neuroprotective and sedative activity of the metabolites
Authors: Green A R , Murray T K , Misra A , Snape M F , Jones J A , Cross A J 
Published: January 2005

A single dose of clomethiazole (600 μmol kg−1 i.p.) has previously been shown to be neuroprotective in the gerbil model of global ischaemia.
In gerbils, clomethiazole (600 μmol kg−1) injection produced a rapid appearance (peak within 5 min) of drug in plasma and brain and similar clearance (plasma t1/2: 40 min) from both tissues. The peak brain concentration (226±56 nmol g−1) was 40% higher than plasma.
One major metabolite, 5‐(1‐hydroxyethyl‐2‐chloro)‐4‐methylthiazole (NLA‐715) and two minor metabolites 5‐(1‐hydroxyethyl)‐4‐methylthiazole (NLA‐272) and 5‐acetyl‐4‐methylthiazole (NLA‐511) were detected in plasma and brain.
Evidence suggested that clomethiazole is metabolized directly to both NLA‐715 and NLA‐272.
Injection of NLA‐715, NLA‐272 or NLA‐511 (each at 600 μmol kg−1) produced brain concentrations respectively 2.2, 38 and 92 times greater than seen after clomethiazole (600 μmol kg−1).
Clomethiazole (600 μmol kg−1) injected 60 min after a 5 min bilateral carotid artery occlusion in gerbils attenuated the ischaemia‐induced degeneration of the hippocampus by approximately 70%. The metabolites were not neuroprotective at this dose.
In mice, clomethiazole (600 μmol kg−1) produced peak plasma and brain concentrations approximately 100% higher than in gerbils, drug concentrations in several brain regions were similar but 35% higher than plasma. Clomethiazole (ED50: 180 μmol kg−1) and NLA‐715 (ED50: 240 μmol kg−1) inhibited spontaneous locomotor activity. The other metabolites were not sedative (ED50 >600 μmol kg−1).
These data suggest that the neuroprotective action of clomethiazole results from an action of the parent compound and that NLA‐715 contributes to the sedative activity of the drug.

British Journal of Pharmacology (2000) 129, 95–100; doi:10.1038/sj.bjp.0703042
Inhibition by troglitazone of the antigen‐induced production of leukotrienes in immunoglobulin E‐sensitized RBL‐2H3 cells
Authors: Yamashita Masamichi , Kushihara Mikie , Hirasawa Noriyasu , Takasaki Wataru , Takahagi Hidekuni , Takayanagi Motoaki , Ohuchi Kazuo 
Published: January 2005

The effect of troglitazone, an anti‐diabetic drug with insulin‐sensitizing action, on antigen‐induced production of leukotriene (LT) B4, C4 and E4 and prostaglandin D2 (PGD2) was examined in dinitrophenol (DNP)‐specific immunoglobulin E (IgE)‐sensitized RBL‐2H3 mast cells following stimulation by the antigen, DNP‐conjugated human serum albumin. Levels of LTB4, C4 and E4 and PGD2 in the conditioned medium were enzyme‐immunoassayed.
Troglitazone inhibited the antigen‐induced production of LTB4, C4 and E4 and the potency of the inhibition was comparable to that of zileuton, a specific inhibitor of 5‐lipoxygenase (5‐LOX) and a clinically used anti‐asthmatic drug. Neither troglitazone nor zileuton affected antigen‐induced production of PGD2, arachidonic acid release from membrane phospholipids and degranulation.
Troglitazone inhibited LTB4 production by the supernatant fraction of RBL‐2H3 cell lysate with similar potency to zileuton, suggesting that troglitazone inhibits LT production by direct inhibition of 5‐LOX activity.
Furthermore, it was shown that troglitazone as well as zileuton inhibited LTB4 production in A23187‐stimulated rat peritoneal neutrophils.
These findings suggest that troglitazone inhibits antigen‐induced LT production in the IgE‐sensitized RBL‐2H3 cells and A23187‐stimulated rat peritoneal neutrophils by direct inhibition of 5‐LOX activity.

British Journal of Pharmacology (2000) 129, 367–373; doi:10.1038/sj.bjp.0703044
Effects of spinally administered P2X receptor agonists and antagonists on the responses of dorsal horn neurones recorded in normal, carrageenan‐inflamed and neuropathic rats
Authors: Stanfa Louise C , Kontinen Vesa K , Dickenson Anthony H 
Published: January 2005

The function and role of P2X receptors in the spinal transmission of nociception was investigated using the selective P2X receptor agonists, α,β‐methylene ATP (α,β‐me ATP) and β,γ‐methylene‐L‐ATP (β,γ‐me‐L‐ATP) and the P2X receptor antagonists pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonate (PPADS) and suramin.
Intrathecal administration of 5 and 50 μg of β,γ‐me‐L‐ATP produced a significant facilitation of the C‐fibre evoked response and a tendency towards increased excitability of the post‐discharge, but not Aβ‐fibre evoked response of dorsal horn neurones recorded in normal animals. Administration of similar doses of α,β‐me ATP did not produce an overall change in the response of the neuronal population.
Peripheral administration of 20 μg of these agonists into the paw of the rat evoked firing in the dorsal horn neurones.
Intrathecal administration of the antagonists, suramin (50 and 500 μg) and PPADS (5, 50 and 500 μg), to normal animals and to animals with a model of neuropathy induced by spinal nerve ligation did not alter the evoked neuronal responses. In contrast, intrathecal administration of 500 μg of suramin to animals 3 h after the induction of carrageenan inflammation produced a significant inhibition of the C‐fibre evoked response of the neurones. Similar inhibitions were also seen following high doses of intrathecal PPADS, although this did not reach significance.
These results suggest that spinal P2X receptors may play a role in the modulation of spinal nociceptive transmission following the development of inflammation, but that these receptors play at most a minor role in spinal nociceptive processing in normal and neuropathic animals.

British Journal of Pharmacology (2000) 129, 351–359; doi:10.1038/sj.bjp.0703047
Stereoselective modulatory actions of oleamide on GABAA receptors and voltage‐gated Na+ channels in vitro: a putative endogenous ligand for depressant drug sites in CNS
Authors: Verdon Bernard , Zheng Jian , Nicholson Russell A , Ganelli C Robin , Lees George 
Published: January 2005

cis‐9,10‐octadecenoamide (‘oleamide’) accumulates in CSF on sleep deprivation. It induces sleep in animals (the trans form is inactive) but its cellular actions are poorly characterized. We have used electrophysiology in cultures from embryonic rat cortex and biochemical studies in mouse nerve preparations to address these issues.
Twenty μM cis‐oleamide (but not trans) reversibly enhanced GABAA currents and depressed the frequency of spontaneous excitatory and inhibitory synaptic activity in cultured networks.
cis‐oleamide stereoselectively blocked veratridine‐induced (but not K+‐induced) depolarisation of mouse synaptoneurosomes (IC50, 13.9 μM).
The cis isomer stereoselectively blocked veratridine‐induced (but not K+‐induced) [3H]‐GABA release from mouse synaptosomes (IC50, 4.6 μM).
At 20 μM cis‐oleamide, but not trans, produced a marked inhibition of Na+ channel‐dependent rises in intrasynaptosomal Ca2+.
The physiological significance of these observations was examined by isolating Na+ spikes in cultured pyramidal neurones. Sixty‐four μM cis‐oleamide did not significantly alter the amplitude, rate of rise or duration of unitary action potentials (1 Hz).
cis‐Oleamide stereoselectively suppressed sustained repetitive firing (SRF) in these cells with an EC50 of 4.1 μM suggesting a frequency‐ or state‐dependent block of voltage‐gated Na+ channels.
Oleamide is a stereoselective modulator of both postsynaptic GABAA receptors and presynaptic or somatic voltage‐gated Na+ channels which are crucial for synaptic inhibition and conduction. The modulatory actions are strikingly similar to those displayed by sedative or anticonvulsant barbiturates and a variety of general anaesthetics.
Oleamide may represent an endogenous modulator for drug receptors and an important regulator of arousal.

British Journal of Pharmacology (2000) 129, 283–290; doi:10.1038/sj.bjp.0703051
An indirect influence of phenylephrine on the release of endothelium‐derived vasodilators in rat small mesenteric artery
Authors: Dora K A , Hinton J M , Walker S D , Garland C J 
Published: January 2005

The possibility that stimulation of smooth muscle α1‐adrenoceptors modulates contraction via the endothelium was examined in rat small mesenteric arteries.
Nω‐nitro‐L‐arginine methyl ester, (L‐NAME, 100 μM to inhibit NO synthase) increased contraction to single concentrations of phenylephrine (1–3 μM) by approximately 2 fold (from a control level of 14.2±3.0 to 34.1±4.2% of the maximum contraction of the artery, n=20). The action of L‐NAME was abolished by disrupting the endothelium.
The subsequent addition of apamin (to inhibit small conductance Ca2+‐activated K+ channels, 50 nM) further augmented phenylephrine contractions, in an endothelium‐dependent manner, to more than 3 fold above control (50.4±5.3% of the maximum contraction, n=11).
Charybdotoxin (non‐selective inhibitor of large conductance Ca2+‐activated K+ channels, BKCa, 50 nM) plus L‐NAME augmented the level of phenylephrine contraction to 4–5‐fold above control (64.1±3.1%, n=5), but this effect was independent of the endothelium. The potentiation of contraction by charybdotoxin could be mimicked with the selective BKCa inhibitor, iberiotoxin,.
Apamin together with L‐NAME and charybdotoxin further significantly increased the phenylephrine contraction by 5–6‐fold, to 79.9±3.5% of the maximum contraction of the artery (n=13).
Phenylephrine failed directly to increase the intracellular Ca2+ concentration in endothelial cells freshly isolated from the small mesenteric artery.
Stimulation of smooth muscle α1‐adrenoceptors in the mesenteric artery induces contraction that is markedly suppressed by the endothelium. The attenuation of contraction appears to reflect both the release of NO from the endothelium and the efflux of K+ from both endothelial and smooth muscle cells. This suggests that the release of NO and endothelium‐derived hyperpolarizing factor can be evoked indirectly by agents which act only on the smooth muscle cells.

British Journal of Pharmacology (2000) 129, 381–387; doi:10.1038/sj.bjp.0703052
Effects of P1 and P2 receptor antagonists on β,γ‐methyleneATP‐ and CGS21680‐induced cyclic AMP formation in NG108‐15 cells
Authors: Ohkubo Satoko , Kimura Junko , Nakanishi Hironori , Matsuoka Isao 
Published: January 2005

We have previously shown that ATP increased cyclic AMP in NG108‐15 cells, which was inhibited by P1 receptor antagonist methylxanthines. In the present study, we examined the effects of P1 and P2 receptor antagonists on cyclic AMP formation induced by β,γ‐methyleneATP (β,γ‐MeATP) and CGS21680, an A2A adenosine receptor agonist, in NG108‐15 cells.
β,γ‐MeATP and CGS21680 increased intracellular cyclic AMP with EC50 values of 8.0±0.98 μM (n=4) and 42±7.5 nM (n=4), respectively.
Several P1 receptor antagonists inhibited both β,γ‐MeATP‐ and CGS21680‐induced cyclic AMP increase with a similar rank order of potency; ZM241385>CGS15943>XAC>DPCPX. However, the pKi values of these antagonists for β,γ‐MeATP were larger than those for CGS21680.
Alloxazine, a P1 receptor antagonist, and several P2 receptor antagonists (PPADS, iPPADS, reactive blue‐2) inhibited β,γ‐MeATP‐induced response, while these antagonists little affected CGS21680‐induced one. Suramin was effective only for β,γ‐MeATP‐induced response at 1 mM.
2‐chloroadenosine (2CADO) and 2‐chloroATP (2ClATP) increased cyclic AMP with similar potencies. The effects of these agonists were both inhibited by ZM241385, but only 2ClATP‐induced response was inhibited by PPADS.
ATP‐ and β,γ‐MeATP‐induced responses were little affected by α,β‐methyleneADP, a 5′‐nucleotidase inhibitor.
These results clearly demonstrate that ATP‐stimulated cyclic AMP formation can be distinguished from the A2A receptor agonist‐induced one by using the several P1 and P2 receptor antagonists.

British Journal of Pharmacology (2000) 129, 291–298; doi:10.1038/sj.bjp.0703053
Different role of IL‐4 in the onset of hapten‐induced contact hypersensitivity in BALB/c and C57BL/6 mice
Authors: Nagai Hiroichi , Ueda Yoshifumi , Ochi Takashi , Hirano Yosuke , Tanaka Hiroyuki , Inagaki Naoki , Kawada Kenji 
Published: January 2005

To study the role of interleukin (IL)‐4 in the onset of contact hypersensitivity (CH) in mice, the effect of IL‐4 gene‐depletion and anti‐IL‐4 monoclonal antibody treatment on dinitrofluorobenzene (DNFB)‐induced CH was examined. Simultaneously, to clarify the effect of background gene, DNFB‐induced CH in BALB/c and C57BL/6 mice was compared.
Five repeated topical applications of DNFB to the ears of mice resulted in CH of the ears in terms of increases in ear thickness and histopathological changes. The magnitude of ear thickness increase in BALB/c mice was almost three times greater than that in C57BL/6 mice.
The CH in BALB/c mice was significantly suppressed by IL‐4 gene‐depletion and anti‐IL‐4 monoclonal antibody treatment. In contrast, the symptoms of dermatitis in C57BL/6 mice were slightly affected by the same treatment. These changes corresponded well to the production of specific IgE antibody.
Total IgE antibody production and the expression of productive Cε mRNA were dramatically suppressed by IL‐4 gene‐depletion and anti‐IL‐4 treatment in BALB/c and C57BL/6 mice. Neither total IgG nor IgM levels in either strain of mice was altered by depletion of IL‐4.
The expression of IFN‐γ in the skin lesion was dramatically suppressed by IL‐4 gene‐depletion in BALB/c mice, but not in C57BL/6 mice.
These findings indicate that IL‐4 plays an important role in the onset of DNFB‐induced CH in BALB/c mice, but not in C57BL/6 mice.

British Journal of Pharmacology (2000) 129, 299–306; doi:10.1038/sj.bjp.0703054
Lipopolysaccharide activates nuclear factor κB in rat intestine: role of endogenous platelet‐activating factor and tumour necrosis factor
Authors: De Plaen Isabelle G , Tan Xiao‐Di , Chang Hong , Wang Liya , Remick Daniel G , Hsueh Wei 
Published: January 2005

We examined the effect of lipopolysaccharide (LPS), a cell wall constituent of Gram negative bacteria, on nuclear factor κB (NF‐κB) activation in the intestine and the roles of endogenous platelet‐activating factor (PAF), tumour necrosis factor‐α (TNF) and neutrophils. We also compared the time course of NF‐κB activation in response to PAF and LPS.
Ileal nuclear extracts from LPS (8 mg kg−1, IV)‐injected rats were assayed for NF‐κB‐DNA‐binding activity and identification of the subunits. Some rats were pretreated with WEB2170 (a PAF receptor antagonist), anti‐TNF antibody, or anti‐neutrophil antiserum. NF‐κB p65 was localized by immunohistochemistry. An additional group was challenged with PAF (2 μg kg−1, IV) for comparison.
LPS activates intestinal NF‐κB, both as p50‐p50 and p50‐p65 dimers within 15 min, and the effect peaks at 2 h. The effect is slower and more sustained than that of PAF, which peaks at 30 min. Activated NF‐κB was immunolocalized within epithelial and lamina propria cells. LPS effect was reduced by 41, 37 and 44%, respectively, in animals pretreated with WEB2170, anti‐TNF antibody, or anti‐neutrophil antiserum (P<0.05).
LPS activates intestinal NF‐κB in vivo and neutrophil activation is involved in its action. The LPS effect is mediated by both endogenous PAF and TNF.

British Journal of Pharmacology (2000) 129, 307–314; doi:10.1038/sj.bjp.0703055
Enhanced nociception by exogenous and endogenous substance P given into the spinal cord in mice lacking NR2A/ε1, an NMDA receptor subunit
Authors: Inoue Makoto , Mishina Masayoshi , Ueda Hiroshi 
Published: January 2005

In capsaicin‐pretreated mice, the nociceptive responses induced by intrathecally (i.t.) administered substance P (SP) were enhanced by N‐methyl‐D‐aspartate (NMDA)‐type receptor antagonists, dizocilpine (MK801) and D‐2‐amino‐5‐phosphonopentanoate (D‐AP5) in a dose‐dependent manner. Similar enhancement of SP‐induced nociception was also observed in mice lacking the NMDA‐type glutamate receptor NR2A/ε1 subunit gene (GluRε1−/− mice). On the other hand, GluRε1−/− mice showed a marked enhancement of the peripheral nociceptive responses induced by intraplantar (i.pl.) injection of SP and bradykinin (BK). As the nociceptive responses to SP and BK (i.pl.) were both antagonized by CP‐99994, an neurokinin1 (NK1) antagonist (i.t.), these results suggest that GluRε1 receptor may play an inhibitory role in the downstream mechanisms of primary nociceptive SP neurones, possibly through activation of unidentified inhibitory neurones.British Journal of Pharmacology (2000) 129, 239–241; doi:10.1038/sj.bjp.0703056
Differential actions of L‐cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta
Authors: Ellis Anthie , Guang Li Chun , Rand Michael J 
Published: January 2005

The effects of L‐cysteine were tested in rat aortic rings on responses to nitric oxide free radical (NO•), nitroxyl (NO−) derived from Angeli's salt and endothelium‐derived relaxing factor (EDRF) activated by acetylcholine, ATP and the calcium ionophore A23187. Concentrations of 300 μM or less of L‐cysteine had no effect on responses.
Relaxations produced by exogenous NO• (0.25–2.5 μM) were markedly prolonged and relaxations produced by sodium nitroprusside (0.001–0.3 μM) were enhanced by 1 and 3 mM L‐cysteine. The enhancements by L‐cysteine of responses to NO• and sodium nitroprusside may be attributed to the formation of S‐nitrosocysteine.
Relaxations mediated by the nitroxyl anion (0.3 μM) donated from Angeli's salt were more prolonged than those produced by NO•, and nitroxyl‐induced relaxations were reduced by L‐cysteine (1 and 3 mM).
EDRF‐mediated relaxations produced by acetylcholine (0.01–10 μM), ATP (3–100 μM) and the calcium ionophore A23187 (0.1 μM) were significantly reduced by 3 mM L‐cysteine.
The similarity between the inhibitory effects of L‐cysteine on responses to EDRF and on those to nitroxyl suggests that a component of the response to EDRF may be mediated by nitroxyl anion.

British Journal of Pharmacology (2000) 129, 315–322; doi:10.1038/sj.bjp.0703058
Functional characterization of the P2X4 receptor orthologues
Authors: Jones C A , Chessell I P , Simon J , Barnard E A , Miller K J , Michel A D , Humphrey P P A 
Published: January 2005

The aim of this study was to functionally characterize the recombinant mouse P2X4 receptor and to compare its pharmacological properties with those of the human and rat orthologues.
Whole cell recordings were made from rafts of HEK‐293 cells stably expressing recombinant mouse, rat or human P2X4 receptors, using Cs‐aspartate containing electrodes (3–8 MΩ) in a HEPES‐buffered extracellular medium.
The agonist potency of ATP at the three species orthologues was similar, with mean EC50 values of 2.3 μM, 1.4 μM and 5.5 μM, respectively.
Adenosine‐5′‐tetraphosphate (AP4) acted as a partial agonist with respect to ATP at the mouse and human P2X4 receptors (EC50=2.6 and 3.0 μM), but was significantly less potent at the rat orthologue (EC50=20.0 μM). α,β‐methylene adenosine‐5′‐triphosphate (α,β‐meATP) also acted as a partial agonist, producing 29% of the maximum response at the mouse P2X4 and 24% at the human P2X4 receptor.
In contrast to the other species orthologues, α,β‐meATP failed to elicit a significant agonist response at rat P2X4 receptors, and was found to act as an antagonist, with an IC50 of 4.6 μM, against 10 μM ATP.
Mouse P2X4 receptors were found to be sensitive to the antagonist, pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) (IC50=10.5 μM), as were human P2X4 receptors (IC50=9.6 μM). The rat receptor however, showed a low sensitivity to PPADS (IC50>100 μM).
All three orthologues were relatively suramin‐insensitive (IC50>100 μM) and insensitive to 1‐[N,O‐Bis(5‐isoquinoline sulphonyl)benzyl]‐2‐(4‐phenylpiperazine)ethyl]‐5‐isoquinoline sulphonamide (KN‐62; IC50>3 μM).
Our results suggest that the pharmacological properties of the mouse receptor are most similar to the human P2X4 receptor, and differ markedly from the rat receptor.

British Journal of Pharmacology (2000) 129, 388–394; doi:10.1038/sj.bjp.0703059
Effects of mefloquine on cardiac contractility and electrical activity in vivo, in isolated cardiac preparations, and in single ventricular myocytes
Authors: Coker Susan J , Batey Andrew J , Lightbown Ian D , Díaz Mary E , Eisner David A 
Published: January 2005

To examine the possible cardiotoxicity of the antimalarial drug mefloquine, increasing doses (0.3–30 mg kg−1) were given i.v. to anaesthetized guinea‐pigs. Mefloquine did not alter ECG intervals significantly but gradually increased systolic blood pressure (at 3 mg kg−1) then had a depressor effect (at 10 mg kg−1). Death due to profound hypotension, probably resulting from cardiac contractile failure or AV block, occurred after either 10 mg kg−1 (2/6) or 30 mg kg−1 (4/6) mefloquine.
In isolated cardiac preparations mefloquine (3–100 μM) did not alter the effective refractory period but at the higher concentrations resting tension increased. Developed tension was reduced by 100 μM mefloquine in left atria (from 5.8±1.7 to 2.2±0.4 mN) whereas in papillary muscles although 30 μM mefloquine reduced developed tension (from 2.6±0.5 to 1.1±0.1 mN) subsequent addition of 100 μM caused a marked, but not sustained, positive inotropic effect (from 1.2±0.1 to 3.8±0.8 mN).
In single ventricular myocytes, mefloquine (10 μM) shortened action potential duration (e.g. APD90 from 285±29 to 141±12 ms) and reduced the amplitude of the systolic Ca2+ transient. These effects were accompanied by a decrease in the L‐type Ca2+ current.
These results indicate that the main adverse effect of mefloquine on the heart is a negative inotropic action. This action can be explained by blockade of L‐type Ca2+ channels.

British Journal of Pharmacology (2000) 129, 323–330; doi:10.1038/sj.bjp.0703060