BenzamilNCX inhibitor; inhibits TRPP3 channel activity CAS# 161804-20-2 |
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Quality Control & MSDS
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Chemical structure
3D structure
Cas No. | 161804-20-2 | SDF | Download SDF |
PubChem ID | 5702295 | Appearance | Powder |
Formula | C13H15Cl2N7O | M.Wt | 356.21 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : ≥ 100 mg/mL (280.73 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown. | ||
Chemical Name | 3,5-diamino-N-(N'-benzylcarbamimidoyl)-6-chloropyrazine-2-carboxamide;hydrochloride | ||
SMILES | C1=CC=C(C=C1)CN=C(N)NC(=O)C2=C(N=C(C(=N2)Cl)N)N.Cl | ||
Standard InChIKey | ZNWMRWWNJBXNKJ-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C13H14ClN7O.ClH/c14-9-11(16)20-10(15)8(19-9)12(22)21-13(17)18-6-7-4-2-1-3-5-7;/h1-5H,6H2,(H4,15,16,20)(H3,17,18,21,22);1H | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Na+/Ca2+ exhanger (NCX) inhibitor (IC50 ~ 100 nM); TRPP3 channel blocker (IC50 = 1.1 μM for inhibition of Ca2+-activated TRPP3 channel activity). Also non-selective Deg/ENaC family blocker; reduces mechanosensitivity of colonic afferents. More potent derivative of amiloride. |
Benzamil Dilution Calculator
Benzamil Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.8073 mL | 14.0367 mL | 28.0733 mL | 56.1467 mL | 70.1833 mL |
5 mM | 0.5615 mL | 2.8073 mL | 5.6147 mL | 11.2293 mL | 14.0367 mL |
10 mM | 0.2807 mL | 1.4037 mL | 2.8073 mL | 5.6147 mL | 7.0183 mL |
50 mM | 0.0561 mL | 0.2807 mL | 0.5615 mL | 1.1229 mL | 1.4037 mL |
100 mM | 0.0281 mL | 0.1404 mL | 0.2807 mL | 0.5615 mL | 0.7018 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response.[Pubmed:23639808]
Am J Physiol Gastrointest Liver Physiol. 2013 Jul 1;305(1):G106-17.
Transient receptor potential (TRP) subfamily M member 5 (TRPM5) cation channel is involved in sensing sweet, bitter, umami, and fat taste stimuli, complex-tasting divalent salts, and temperature-induced changes in sweet taste. To investigate if the amiloride- and Benzamil (Bz)-insensitive NaCl chorda tympani (CT) taste nerve response is also regulated in part by TRPM5, CT responses to 100 mM NaCl + 5 muM Bz (NaCl + Bz) were monitored in Sprague-Dawley rats, wild-type (WT) mice, and TRP vanilloid subfamily member 1 (TRPV1) and TRPM5 knockout (KO) mice in the presence of resiniferatoxin (RTX), a TRPV1 agonist. In rats, NaCl + Bz + RTX CT responses were also monitored in the presence of triphenylphosphine oxide, a specific TRPM5 blocker, and capsazepine and N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791), specific TRPV1 blockers. In rats and WT mice, RTX produced biphasic effects on the NaCl + Bz CT response, enhancing the response at 0.5-1 muM and inhibiting it at >1 muM. The NaCl + Bz + SB-366791 CT response in rats and WT mice and the NaCl + Bz CT response in TRPV1 KO mice were inhibited to baseline level and were RTX-insensitive. In rats, blocking TRPV1 by capsazepine or TRPM5 by triphenylphosphine oxide inhibited the tonic NaCl + Bz CT response and shifted the relationship between RTX concentration and the magnitude of the tonic CT response to higher RTX concentrations. TRPM5 KO mice elicited no constitutive NaCl + Bz tonic CT response. The relationship between RTX concentration and the magnitude of the tonic NaCl + Bz CT response was significantly attenuated and shifted to higher RTX concentrations. The results suggest that pharmacological or genetic alteration of TRPM5 activity modulates the Bz-insensitive NaCl CT response and its modulation by TRPV1 agonists.
Benzamil sensitive ion channels contribute to volume regulation in canine chondrocytes.[Pubmed:22928819]
Br J Pharmacol. 2013 Apr;168(7):1584-96.
BACKGROUND AND PURPOSE: Chondrocytes exist within cartilage and serve to maintain the extracellular matrix. It has been postulated that osteoarthritic (OA) chondrocytes lose the ability to regulate their volume, affecting extracellular matrix production. In previous studies, we identified expression of epithelial sodium channels (ENaC) in human chondrocytes, but their function remained unknown. Although ENaC typically has Na(+) transport roles, it is also involved in the cell volume regulation of rat hepatocytes. ENaC is a member of the degenerin (Deg) family, and ENaC/Deg-like channels have a low conductance and high sensitivity to Benzamil. In this study, we investigated whether canine chondrocytes express functional ENaC/Deg-like ion channels and, if so, what their function may be. EXPERIMENTAL APPROACH: Canine chondrocytes were harvested from dogs killed for unassociated welfare reasons. We used immunohistochemistry and patch-clamp electrophysiology to investigate ENaC expression and video microscopy to analyse the effects of pharmacological inhibition of ENaC/Deg on cell volume regulation. KEY RESULTS: Immunofluorescence showed that canine chondrocytes expressed ENaC protein. Single-channel recordings demonstrated expression of a Benzamil-sensitive Na(+) conductance (9 pS), and whole-cell experiments show this to be approximately 1.5 nS per cell with high selectivity for Na(+) . Benzamil hyperpolarized chondrocytes by approximately 8 mV with a pD2 8.4. Chondrocyte regulatory volume decrease (RVI) was inhibited by Benzamil (pD2 7.5) but persisted when extracellular Na(+) ions were replaced by Li(+) . CONCLUSION AND IMPLICATIONS: Our data suggest that Benzamil inhibits RVI by reducing the influx of Na(+) ions through ENaC/Deg-like ion channels and present ENaC/Deg as a possible target for pharmacological modulation of chondrocyte volume.
Antinociceptive effects of amiloride and benzamil in neuropathic pain model rats.[Pubmed:23960454]
J Korean Med Sci. 2013 Aug;28(8):1238-43.
Amiloride and Benzamil showed antinocicepitve effects in several pain models through the inhibition of acid sensing ion channels (ASICs). However, their role in neuropathic pain has not been investigated. In this study, we investigated the effect of the intrathecal amiloride and Benzamil in neuropathic pain model, and also examined the role of ASICs on modulation of neuropathic pain. Neuropathic pain was induced by L4-5 spinal nerve ligation in male Sprague-Dawley rats weighing 100-120 g, and intrathecal catheterization was performed for drug administration. The effects of amiloride and Benzamil were measured by the paw-withdrawal threshold to a mechanical stimulus using the up and down method. The expression of ASICs in the spinal cord dorsal horn was also analyzed by RT-PCR. Intrathecal amiloride and Benzamil significantly increased the paw withdrawal threshold in spinal nerve-ligated rats (87%+/-12% and 76%+/-14%, P=0.007 and 0.012 vs vehicle, respectively). Spinal nerve ligation increased the expression of ASIC3 in the spinal cord dorsal horn (P=0.01), and this increase was inhibited by both amiloride and Benzamil (P<0.001 in both). In conclusion, intrathecal amiloride and Benzamil display antinociceptive effects in the rat spinal nerve ligation model suggesting they may present an alternative pharmacological tool in the management of neuropathic pain at the spinal level.
The neurogenic phase of angiotensin II-salt hypertension is prevented by chronic intracerebroventricular administration of benzamil.[Pubmed:24744909]
Physiol Rep. 2014 Feb 26;2(2):e00245.
Hypertension induced by chronic administration of angiotensin II (AngII) is exacerbated by high-salt intake. Previous studies have demonstrated that this salt-sensitive component is due to increased activity of the sympathetic nervous system, suggesting an interaction of plasma AngII with sodium-sensitive regions of the brain. This study tested the hypothesis that the salt-sensitive component of AngII-induced hypertension would be prevented by intracerebroventricular (ICV) administration of the sodium channel/transporter blocker Benzamil. Male Sprague Dawley rats were instrumented to measure mean arterial pressure (MAP) by radio telemetry and for ICV administration of Benzamil or vehicle and placed in metabolic cages for measurement of sodium and water intake and excretion. In rats consuming a high-salt diet (2.0% NaCl) and treated with ICV vehicle, administration of AngII (150 ng/kg/min, sc) for 13 days increased MAP by ~30 mmHg. ICV administration of Benzamil (16 nmol/day) had no effect during the first 5 days of AngII, but returned MAP to control levels by Day 13. There were minimal or no differences between ICV vehicle or Benzamil groups in regards to sodium and water balance. A lower dose of ICV Benzamil administered ICV at 8 nmol/day had no effect on the MAP response to AngII in rats on a high-salt diet. Finally, in contrast to rats on a high-salt diet, AngII had negligible effects on MAP in rats consuming a low-salt diet (0.1% NaCl) and there were no differences in any variable between ICV Benzamil (16 nmol/day) and ICV vehicle-treated groups. We conclude that the salt-sensitive component of AngII-induced hypertension is dependent on Benzamil blockable sodium channels or transporters in the brain.
Inhibition of TRPP3 channel by amiloride and analogs.[Pubmed:17804601]
Mol Pharmacol. 2007 Dec;72(6):1576-85.
TRPP3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a Ca2+-activated channel permeable to Ca2+, Na+, and K+. TRPP3 has been implicated in sour tasting in bipolar cells of tongue and in regulation of pH-sensitive action potential in spinal cord neurons. TRPP3 is also present in excitable and nonexcitable cells of other tissues, including retina, brain, heart, testis, and kidney, with unknown functions. In this study, we examined the functional modulation of TRPP3 channel by amiloride and its analogs, known to inhibit several ion channels and transporters and respond to all taste stimuli, using Xenopus laevis oocyte expression, electrophysiology, and radiotracer measurements. We found that amiloride and its analogs inhibit TRPP3 channel activities with different affinities. Radiolabeled (45)Ca2+ uptake showed that TRPP3-mediated Ca2+ transport was inhibited by amiloride, phenamil, Benzamil, and 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Two-microelectrode voltage clamp experiments revealed that TRPP3-mediated Ca2+-activated currents are substantially inhibited by amiloride analogs, in an order of potency of phenamil > Benzamil > EIPA > amiloride, with IC50 values of 0.14, 1.1, 10.5, and 143 microM, respectively. The inhibition potency positively correlated with the size of inhibitors. Using cell-attached patch clamping, we showed that the amiloride analogs decrease the open probability and mean open time but have no effect on single-channel conductance. Study of inhibition by phenamil in the presence of previously reported inhibitor tetrapentylammonium indicates that amiloride and organic cation inhibitors compete for binding the same site on TRPP3. TRPP3 may contribute to previously reported in vivo amiloride-sensitive cation transport.
Acid sensing ion channels 2 and 3 are required for inhibition of visceral nociceptors by benzamil.[Pubmed:17467171]
Pain. 2007 Dec 15;133(1-3):150-60.
The Deg/ENaC family of ion channels, including ASIC1, 2 and 3, are candidate mechanotransducers in visceral and somatic sensory neurons, although each channel may play a different role in different sensory pathways. Here we determined which distinct populations of visceral sensory neurons are sensitive to the non-selective Deg/ENaC blocker Benzamil, and which ASIC channels are targets for Benzamil by studying its actions in knockout mice. Single afferent fiber recordings were made in vitro from mouse high threshold colonic thoracolumbar splanchnic afferents and low threshold gastroesophageal vagal afferents. mRNA expression of ASIC subtypes was compared between colonic and gastroesophageal afferents by quantitative RT-PCR of transcripts following laser capture microdissection of retrogradely labeled cell bodies. Mechanosensitivity of colonic afferents was potently reduced by Benzamil (10(-6)-3 x 10(-4)M), whereas gastroesophageal afferents were marginally inhibited. Inhibition of colonic afferent mechanosensitivity by Benzamil was markedly diminished in ASIC2-/- and ASIC3-/- mice, but unchanged in ASIC1a-/-. Therefore ASIC2 and 3 are targets for Benzamil to inhibit colonic afferent mechanosensitivity. Conversely, gastroesophageal afferents are less sensitive to Benzamil, and its action depends less on ASIC expression. mRNA for ASIC3 showed higher and ASIC1a showed lower relative expression in colonic afferents from thoracolumbar dorsal root ganglia than in gastric afferents from nodose (vagal) ganglia. These data indicate that ASICs on colonic afferents present distinct pharmacological targets for visceral pain.
Characterization of a Na(+)-Ca(2+) exchanger in podocytes.[Pubmed:12270979]
Nephrol Dial Transplant. 2002 Oct;17(10):1742-50.
BACKGROUND: Knowledge about Ca(2+) extrusion mechanisms in podocytes is limited. The aim of the study was to test whether a Na(+)-Ca(2+) exchanger (NCX) is present in differentiated podocytes and if so to examine its regulatory properties. METHODS: Intracellular Ca(2+) concentration ([Ca(2+)](i)) and intracellular pH were measured microspectrofluorometrically in single podocytes. Expression of NCX mRNA was studied by reverse transcription-polymerase chain reaction. NCX protein expression was investigated by immunocytochemistry. RESULTS: Substitution of extracellular Na(+) (from 145 to 0, 5, 10, 20, and 30 mM) with N-methyl-D-glucamine resulted in a Na(+) concentration-dependent, reversible increase of [Ca(2+)](i). Complete extracellular Na(+) substitution (0 Na(+)) increased [Ca(2+)](i) reversibly from 95+/-5 to 275+/-16 and back to 66+/-5 nM (n=205). Raising the intracellular Na(+) concentration by application of 50 micro M monensin increased [Ca(2+)](i) from 105+/-22 to 192+/-45 nM (n=12). The [Ca(2+)](i) response induced by a low Na(+) concentration required extracellular Ca(2+) and did not correlate with changes of intracellular pH. The effect was blocked by the NCX inhibitor Benzamil (IC(50) approximately 100 nM). Neither flufenamate (100 micro M, n=6), a blocker of non-selective cation channels, nor Hoe 694 (1 micro M, n=6), an inhibitor of the Na(+)-H(+) exchanger, did significantly influence the [Ca(2+)](i) response induced by extracellular Na(+) depletion. Activation of protein kinase C (PKC) by short-term application (5 min) of phorbol 12-myristate-13-acetate (PMA; 10 nM, n=4; 100 nM, n=7) inhibited Na(+)-Ca(2+) exchange, whereas PKC inhibition by long-term incubation (24 h) with PMA (100 nM, n=9) or bisindolylmaleimide I (100 nM, n=11) both increased Na(+)-Ca(2+) exchange, respectively. Expression of NCX mRNA was detected both in cultured differentiated podocytes and in podocytes directly pulled off from glomeruli ex vivo. NCX protein expression was detected by immunocytochemistry. In a different series of experiments, we studied the potential involvement of the exchanger in podocyte injury induced by the aminonucleoside puromycin. Pre-treatment of podocytes with 0.3 mM puromycin for 24 h significantly reduced the [Ca(2+)](i) response induced by extracellular Na(+) depletion (n=56). Compared with mRNA expression of the housekeeping gene GAPDH, NCX mRNA expression was significantly reduced by puromycin. CONCLUSION: Our results demonstrate the presence of a Na(+)-Ca(2+) exchanger in podocytes and its regulation by PKC. Inhibition of Na(+)-Ca(2+) exchange by puromycin may contribute to podocyte injury in PAN nephrosis.