Ketanserin (tartrate)
(Synonyms: 酒石酸酮色林,R41468 tartrate) 目录号 : GC43999
A potent 5-HT2 receptor antagonist
Cas No.:83846-83-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment: |
The established HEK 293 cell line stably expressing hERG channels is cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% foetal bovine serum, 400 μg/mL G418. The HEK 293 cell line stably expressing recombinant human cardiac KCNQ1/KCNE1 channel current (IKs) is maintained in DMEM containing 10% foetal bovine serum and 100 μg/mL hygromycin. Cells used for electrophysiology are seeded on a glass coverslip. The mutant hERG channels are constructed, and are transiently expressed in HEK 293 cells using 10 μL of Lipofectamine 2000 with 4 μg of hERG mutant cDNA in pCDNA3 vector[1]. |
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Animal experiment: |
Rat[4]A total of 155 specific-pathogen-free 2-month-old male Sprague-Dawley rats, weighing 180-220 g, are used. The rats are randomly divided into the following six groups: 5-HT1A receptor agonist (8-OH-DPAT) PS group (DPAT-PS group, n=30); 5-HT1A receptor antagonist (MDL73005) PS group (MDL-PS group, n=30); 5-HT2A receptor agonist (DOI) PS group (DOI-PS group, n=30); 5-HT2A receptor antagonist (Ketanserin) PS group (Ketan-PS group, n=30); the solvent control no-stress group (0.9% physiological saline group, CON group); and the PS only group (PS group, n=30). The DPAT-PS, MDL-PS, DOI-PS, Ketan-PS and PS groups are further divided into six subgroups (n=5 each) according to the time between the stress and analysis; immediately after stress, and 0.5, 1, 2, 6 and 24 hours after stress. The CON group (n=5) receive normal feed. For the Ketan-PS group, Ketanserin, dissolved in 0.9% physiological saline, is injected intraperitoneally at 5 mg/kg at 1 hour before each stress exposure. |
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References: [1]. Tang Q, et al. The 5-HT2 antagonist Ketanserin is an open channel blocker of human cardiac ether-à-go-go-related gene (hERG) potassium channels. Br J Pharmacol. 2008 Oct;155(3):365-73. |
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Ketanserin tartrate is a selective 5-HT receptor antagonist. Ketanserin tartrate also blocks hERG current (IhERG) in a concentration-dependent manner (IC50=0.11 μM).
Ketanserin at 0.3 μM inhibits the voltage-dependent step current (IhERG.step) and tail current (IhERG.tail) of hERG channels with a 5-min exposure[1]. The synergistic effect observed for AA with 5-HT is, also, blocked by the 5-HT receptor blockers cyproheptadine (IC50=22.0±7 μM), Ketanserin (IC50=152±23 μM). Ketanserin (50-350 μM) inhibits the synergism by blocking the receptor in a dose-dependent manner. The IC50 value of Cyproheptadine is 22±7 μM and Ketanserin is 152±23 μM[2]. Ketanserin inhibits platelet aggregation with an IC50 of 240 (169-339) nM[3].
Ketanserin is a 5-HT2A receptor antagonist. Ketanserin significantly reduces BDNF protein levels in numerous brain regions (CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and midbrain periaqueductal gray). 5-HT2A antagonist Ketanserin can significantly reduce BDNF mRNA levels in various brain regions[4].
References:
[1]. Tang Q, et al. The 5-HT2 antagonist Ketanserin is an open channel blocker of human cardiac ether-à-go-go-related gene (hERG) potassium channels. Br J Pharmacol. 2008 Oct;155(3):365-73.
[2]. Khan N, et al. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists. Drug Des Devel Ther. 2015 Jul 6;9:3497-506.
[3]. Kekewska A, et al. Antiserotonergic properties of terguride in blood vessels, platelets, and valvular interstitial cells. J Pharmacol Exp Ther. 2012 Feb;340(2):369-76.
[4]. Jiang DG, et al. Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress. Neural Regen Res. 2016 Sep;11(9):1471-1479.
| Cas No. | 83846-83-7 | SDF | |
| 别名 | 酒石酸酮色林,R41468 tartrate | ||
| Canonical SMILES | O=C1N(CCN2CCC(C(C3=CC=C(F)C=C3)=O)CC2)C(C4=CC=CC=C4N1)=O.OC([C@H](O)[C@@H](O)C(O)=O)=O | ||
| 分子式 | C22H22FN3O3•C4H6O6 | 分子量 | 545.5 |
| 溶解度 | DMF: 25 mg/ml,DMSO: 25 mg/ml,DMSO:PBS (pH 7.2)(1:9): 0.1 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8332 mL | 9.1659 mL | 18.3318 mL |
| 5 mM | 0.3666 mL | 1.8332 mL | 3.6664 mL |
| 10 mM | 0.1833 mL | 0.9166 mL | 1.8332 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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1. 首先保证母液是澄清的；
2.
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Effect of Ketanserin tartrate on HMG CoA reductase and LDL receptor activity in cultured human skin fibroblasts
Eur J Clin Pharmacol 1990;39(3):217-20.PMID:2257855DOI:10.1007/BF00315099.
In man Ketanserin tartrate reduces plasma LDL cholesterol. To clarify the mechanism of this effect the effect of Ketanserin on 3-hydroxy-3-methylglutaryl (HMG) CoA reductase and LDL receptor activity in cultured human skin fibroblasts has been examined. After incubation with Ketanserin for 14 h HMG CoA reductase activity was decreased in a dose-dependent manner up to 300 ng/ml (550 nM) without changing the free cholesterol content in the cells. Ketanserin increased specific binding and specific internalization of 125I-LDL dose-dependently. There was a significant inverse relationship between the percentage changes in HMG CoA reductase and LDL receptor activity. It appears that Ketanserin induces up-regulation of LDL receptor activity by direct suppression of HMG CoA reductase, and this may be one mechanism by which plasma LDL-cholesterol is reduced by Ketanserin.
Effects of Ketanserin tartrate on 3-hydroxy, 3-methylglutaryl coenzyme A reductase activity in cultured human skin fibroblasts
Cardiovasc Drugs Ther 1990 Jan;4 Suppl 1:69-72.PMID:1981023DOI:10.1007/BF00053430.
Ketanserin tartrate (Ketanserin) is a new antihypertensive drug that is a selective 5HT2 serotonergic receptor antagonist and at high concentrations antagonizes the alpha 1-adrenergic receptor. Several reports have indicated that Ketanserin clinically decreases plasma low density lipoprotein (LDL) cholesterol. In order to clarify the mechanisms of this LDL cholesterol reduction by Ketanserin, we investigated the effects of Ketanserin on 3-hydroxy, 3-methylglutaryl coenzyme A(HMG CoA) reductase activity to cultured human skin fibroblasts. We also studied the effects of ritanserin (a 5HT2 serotonergic receptor antagonist) and prazosin HCl (an alpha 1-adrenergic receptor antagonist) on HMG CoA reductase activity in cultured human skin fibroblasts. Human skin fibroblasts were cultured in Dulbecco's modified Eagle's (DME) medium containing 10% fetal calf serum. Before the cells reached confluence, the medium was changed to DME containing 10% lipoprotein-deficient serum. After incubation for 48-72 hours, the drugs under investigation were added to the medium. The cells were incubated for 14 hours and harvested after washing with phosphate buffered saline. In our study, Ketanserin decreased HMG CoA reductase activity in a dose-dependent manner up to 300 ng/ml (550 nM). Prazosin also decreased HMG CoA reductase activity in a dose-dependent manner up to 40 ng/ml (95 nM); ritanserin decreased HMG CoA reductase activity at concentrations of 100 nM and 200 nM. These findings suggest that the combination of alpha 1-adrenergic receptor and 5HT2 serotonergic receptor antagonist effects of Ketanserin inhibits HMG CoA reductase activity and that this suppression is probably one of the mechanisms for the plasma LDL cholesterol reduction resulting from Ketanserin treatment.
Effects of Ketanserin tartrate on serum lipids in patients with essential hypertension
Drugs 1988;36 Suppl 1:25-34.PMID:3071460DOI:10.2165/00003495-198800361-00006.
Several antihypertensive agents such as thiazide diuretics and some beta-blockers have recently been shown to adversely affect lipid metabolism. Moreover, there is a growing suspicion that the adverse effect on plasma lipids might outweigh the favourable effect of lowering blood pressure. The effect of Ketanserin tartrate (20 to 60 mg daily), a new antihypertensive drug, on blood lipids was evaluated in a 12-week non-comparative clinical trial in 34 patients with mild or moderate hypertension. Ketanserin reduced systolic and diastolic blood pressure by 12.2 and 9.8%, respectively, without altering heart rates. Total cholesterol and low density lipoprotein (LDL)-cholesterol levels in the fasting plasma were observed to decrease significantly by 6.3 and 8.8% respectively, whereas mean triglyceride and high density lipoprotein (HDL)-cholesterol remained almost unchanged. These changes were consistent irrespective of their initial values. Significant decrease in apolipoprotein B and E was also observed. Apolipoprotein A-I, A-II, C-II and C-III were not altered significantly. It is speculated that Ketanserin affects mainly LDL-cholesterol. Based on these findings, Ketanserin is considered to have a potentially beneficial effect on coronary risk profile and should be given full consideration when drug therapy is selected for patients with mild to moderate hypertension.
Anti-aggregation effect of aroxyalkyl derivatives of 2-methoxyphenylpiperazine is due to their 5-HT2A and α2-adrenoceptor antagonistic properties. A comparison with Ketanserin, sarpogrelate, prazosin, yohimbine and ARC239
Eur J Pharmacol 2018 Jan 5;818:263-270.PMID:29111111DOI:10.1016/j.ejphar.2017.10.053.
Serotonin (5-HT) and adrenaline acting at platelet 5-HT2A-serotoninergic and α2-adrenergic receptors are involved in platelet aggregation. We have evaluated the antagonistic potency at 5-HT2A, α2A-, and α2B-adrenoceptors as well as an anti-aggregation effect of aroxyalkyl derivatives of 2-methoxyphenylpiperazine and compared them with Ketanserin, sarpogrelate, prazosin, yohimbine and ARC239 (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione). Functional bioassays at cells expressing human receptors, revealed studied compounds to be moderate antagonists of 5-HT2A and α2-adrenoceptors, with around 2-7 times stronger antagonistic effect at α2B subtype than α2A subtype. Further, studied compounds inhibited 5-HT2A-mediated contraction in isolated rat aortic rings and 5-HT vasopressor response in rat in vivo. Studied compounds inhibited collagen stimulated whole rat blood aggregation with compound MH-77 (1-[(2,3-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride) being more potent than sarpogrelate or yohimbine. They also inhibited 5-HT/adrenaline-, amplified ADP- or collagen- induced platelet aggregation. Simultaneous, moderate blockade of 5-HT2A serotonin and α2-adrenergic receptors is effective in preventing aggregation and could constitute alternative antiplatelet therapy.
Absorption, metabolism and excretion of Ketanserin in man after oral administration
Arzneimittelforschung 1988 Jun;38(6):789-94.PMID:3178919doi
The absorption, metabolism and excretion of Ketanserin [+)-3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4(1H,3H)- quinazolinedione, R 41 468), a novel serotonin S2-receptor antagonist used in hypertension, was studied after a single oral dose of 14C-ketanserin tartrate in three healthy subjects. Absorption from the gastrointestinal tract was rapid and almost complete. The excretion of radioactivity amounted to about 90% after 4 days and was more abundant in urine (68%) than in faeces (24%). Ketone reduction and oxidative N-dealkylation at the piperidine nitrogen were by far the two main metabolic pathways. The former pathway resulted in ketanserin-ol, the main metabolite in plasma as well as in urine (24% of dose) and faeces (5%), the latter pathway in the urinary metabolite 1,4-dihydro-2,4-dioxo-3(2H)quinazolineacetic acid (20%). Other pathways were aromatic hydroxylation at the quinazolinedione moiety and the formation of ether glucuronides. None of the metabolites substantially contributes to the overall pharmacological activity of Ketanserin. The metabolic pathways of Ketanserin in man were identical to those revealed previously in rats and dogs, but the mass balance of the major metabolites resembled more that in dogs than that in rats.