Ketanserin is a serotonin S2-receptor antagonist introduced for the treatment of arterial hypertension and vasospastic disorders. Following oral administration ketanserin is almost completely (more than 98%) and rapidly absorbed and peak concentrations in plasma are reached within 0.5 to 2 hours. Following intravenous administration plasma ketanserin concentrations decay triexponentially with sequential half-lives of 0.13, 2 and 14.3 h[3]. Ketanserin, a selective 5-HT receptor antagonist, prolongs the QT interval of ECG in patients. Ketanserin blocked hERG current (I(hERG)) in a concentration-dependent manner (IC50=0.11 mM). The drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between +10 to +60 mV. Voltage-dependence for inactivation of hERG channels was negatively shifted by 0.3 mM ketanserin. A 2.8 fold attenuation of inhibition by elevation of external K+ concentration (from 5.0 to 20 mM) was observed, whereas the inactivation-deficient mutants S620T and S631A had the IC50s of 0.84 +/- 0.2 and 1.7 +/-0.4 mM (7.6 and 15.4 fold attenuation of block)[4]. It also inhibits the effects of serotonin on platelets in cardiovascular disease, inhibits vasoconstriction caused by the amine, and when administered intravenously improves some haemorheological indices in patients with ischaemic diseases. Administered intravenously, ketanserin 10mg followed by an infusion of 2 to 4 mg/h controls moderate to severe pre- and postoperative hypertension in most patients, acting as a balanced vasodilator, lowering cardiac pre- and afterload{{Brogden RN, Sorkin EM. Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. Drugs. 1990;40(6):903‐949|https://
www.ncbi. nlm.nih.gov/ pubmed/2079001}}.
Ketanserin/凯他色林 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bone-marrow-derived macrophages (BMDMs)
10^-9 M
2 days
Macrophages conditioned with Ketanserin showed a lower pro-fibrotic phenotype in a co-culture system with mesenchymal cells and reduced Col1a1 expression.
Exp Mol Med. 2018 Jul 19;50(7):1-13.
Spleen cells
25 nM
Ketanserin, a specific antagonist of the 5-HT2A receptor, significantly reduced the number of osteoclasts in WT spleen cell cultures.
Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2567-72.
18-81 pre-B cell line
1-10 μM
10-15 min
Ketanserin, a specific antagonist of 5-HT2 receptors, was used to study the effects of 5-HT on potassium currents. Results showed that Ketanserin had no significant effect on 5-HT-induced changes in current amplitude or inactivation rate, indicating that 5-HT2 receptors are not involved in the modulation.
Proc Natl Acad Sci U S A. 1988 Jun;85(12):4557-61.
Ketanserin/凯他色林 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
SERTKO and wild-type mice
Intraperitoneal injection
1 mg/kg/day
Daily for 5 days
Ketanserin almost eliminated apoptosis in SERTKO mice and significantly reduced villus height, crypt depth, and crypt proliferation index.
Gastroenterology. 2012 Aug;143(2):408-17.e2
Mice
Genetically mast cell-deficient mouse model
In vitro administration
10^-5 M
At least 15 minutes
In normal mice, ketanserin significantly inhibited the first phase of the antigen-induced Isc response, but had no significant effect in mast cell-deficient mice.
J Clin Invest. 1991 Feb;87(2):687-93
C57BL/6 mice
30% TBSA thermal injury model
Intraperitoneal injection
10 mg/kg
Daily administration for 21 days (7 days pre-injury and 14 days post-injury)
Ketanserin reduced portal fibrosis in thermally injured mice by modulating the phenotype of macrophages away from their pro-fibrotic state.
Exp Mol Med. 2018 Jul 19;50(7):1-13.
Mice
Chronic multimodal stress model
Intraperitoneal injection
2 mg/kg
Single injection, 60 minutes before psilocybin administration
To test whether ketanserin could block the antidepressant-like behavioral responses to psilocybin. Results showed that ketanserin pretreatment did not prevent the anti-anhedonic effects of psilocybin.
Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2022489118
Mice
Maternal immune activation (MIA) model
Intraperitoneal injection
2 mg/kg
Daily for 7 days
Chronic ketanserin treatment reduces DOI-induced head twitching in MIA offspring
Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):E2492-500
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