Perioperative acute hypertensionâ€”role of Clevidipine butyrate

Kurnutala, Lakshmi N; Soghomonyan, Suren; Bergese, Sergio D.

doi:10.3389/fphar.2014.00197

Cited by 4 publications

(3 citation statements)

References 49 publications

(60 reference statements)

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“…Various modulators can potentiate or block calcium entry through L-type calcium channels. [4][5][6] Calcium antagonists have a versatile pharmacological activity such as antihypertensive and antianginal, [7][8][9] antitumor, 10,11) anti-inflammatory, 12,13) antitubercular, 14,15) anticonvulsant and antithrombotic. 16,17) 1,4-DHPs bind selectively to L-type calcium channel protein, precisely at the transmembrane domain IIIS6 and IVS6 regions of the α1 subunit.…”

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confidence: 99%

Synthesis, Docking Simulation, Biological Evaluations and 3D-QSAR Study of 1,4-Dihydropyridines as Calcium Channel Blockers

El‐Moselhy

Sidhom

Esmat

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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Resurgence to target L-type voltage-dependent calcium channels has been applied by the synthesis of two series of nifedipine analogues where the ortho-or a meta-nitrophenyl ring is retained. A pre-synthetic molecular docking study with a receptor model followed by molecular alignment has been performed on 47 compounds to predict the most active member. The IC 50 values revealed that some of the compounds are similar to or more active than nifedipine. Substitution of groups at the 3-and 5-positions of the dihydropyridine (DHP) ring gave 3k, which is more active than nifedipine. Our valid three-dimensional quantitative structure-activity relationship (3D-QSAR) model prefigures the influence of lipophilicity, bulkiness and chelating effects of the C3 and C5 substituents. Bulky groups interfere with ring-to-ring hydrophobic interaction with tyrosine (Tyr) 4311 and limit the efficiency of increasing the length of the hydrocarbon chain of esters at the 3-and 5-positions of the DHP ring as an approach to increasing the activity. The presence of a chelating substituent on the phenyl ring at the 4-position of the DHP ring ensures strong binding to the receptor and hence stabilization of the closed-channel conformation. The validation of 3D-QSAR model indicated its proficiency in predicting activity of newly compounds belonging to the same chemical class.Key words calcium channel; dihydropyridine; docking; synthesis; three-dimensional quantitative structureactivity relationship (3D-QSAR) Precise regulation of calcium homeostasis is crucial for many physiological functions.1) Divergent types of calcium channels and pumps can control the influx of calcium ions into cells.2,3) Consequently, targeting calcium channels is advantageously beneficial to yield useful drugs. Ca V 1.2 blockers can be roughly categorized into three different chemical classes: 1,4-dihydropyridine (DHP) derivatives, phenylalkylamine derivatives and benzothiazepine derivatives. Among them, DHP derivatives have the most significant pharmacological importance. For example, amlodipine is among the top-five best selling drugs in the treatment of cardiovascular diseases. Various modulators can potentiate or block calcium entry through L-type calcium channels. [4][5][6] Calcium antagonists have a versatile pharmacological activity such as antihypertensive and antianginal, 7-9) antitumor, 10,11) anti-inflammatory, 12,13) antitubercular, 14,15) anticonvulsant and antithrombotic. 16,17) 1,4-DHPs bind selectively to L-type calcium channel protein, precisely at the transmembrane domain IIIS6 and IVS6 regions of the α1 subunit.18) The twelve approved DHP calcium antagonists developed are vasodilators.19) Vasodilatation is due to the uncoupling of the contractile mechanism of vascular smooth muscle, which requires Ca 2+ . 20)Structure-activity relationship (SAR) of DHP 21) and the clinical usage of nifedipine have promoted us to synthesize two series of nifedipine analogues where the ortho-or a meta-nitrophenyl ring is retained. A pre-synthetic molecular docking st...

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confidence: 99%

Synthesis, Docking Simulation, Biological Evaluations and 3D-QSAR Study of 1,4-Dihydropyridines as Calcium Channel Blockers

El‐Moselhy

Sidhom

Esmat

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Hypertensive emergencies usually require the intravenous administration of antihypertensive drugs ( Kurnutala et al, 2014 ). Esmolol is a super short-acting selective beta antagonist.…”

Section: Discussionmentioning

confidence: 99%

Adverse Cardiovascular Effects of Phenylephrine Eye Drops Combined With Intravenous Atropine

Pang

Deng

et al. 2021

Front. Pharmacol.

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Background: Phenylephrine and atropine can cause serious adverse effects when applied in combination. We investigated the effect of phenylephrine eye drops combined with intravenous atropine on the cardiovascular system in patients under general anesthesia undergoing intraocular surgery.Methods: The effects of the drugs were observed through clinical study. Thirteen patients undergoing intraocular surgery under general anesthesia were observed in this study; all were injected intravenously with atropine due to the oculocardiac reflex during surgery. To study the combination of drugs, an in vivo study was performed on rats. Seventy-two standard deviation rats that received phenylephrine eye drops and intravenous atropine treatment under general anesthesia were assessed, of which 18 treated with these drugs simultaneously were administered normal saline, neostigmine or esmolol. Blood pressure and heart rate were recorded and analyzed.Findings: The age of the patients ranged from seven to 14 years old with an average age of 10.7 years old, and 11 patients were male. In patients, 5% phenylephrine eye drops combined with intravenous atropine led to a significant heart rate increase and the increase lasted 20 min. The significant increase in diastolic blood pressure and systolic blood pressure lasted for 15 and 25 min, respectively. From five to 25 min after intravenous atropine treatment, the systolic blood pressure and diastolic blood pressure were both more than 20% higher than that at baseline. In rats, the changes in blood pressure and heart rate were independent of the phenylephrine and atropine administration sequence but were related to the administration time interval. The neostigmine group showed a significant decrease in blood pressure after the increase from the administration of phenylephrine and atropine.Interpretation: Phenylephrine eye drops combined with intravenous atropine have obvious cardiovascular effects that can be reversed by neostigmine. This drug combination should be used carefully for ophthalmic surgery, especially in patients with cardio-cerebrovascular diseases.

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“…CaV1.2 blockers can be roughly categorized into three different chemical classes: 3,4-dihydropyrimidine-2-one (DHP) derivatives, phenylalkylamine derivatives and benzothiazepine derivatives. Calcium antagonists have a versatile pharmacological activity such as antihypertensive and antianginal, antitumor, anti-inflammatory, antitubercular, anticonvulsant and antithrombotic [9][10][11][12][13][14][15][16][17][18][19]. The target key intermediate 3,4-dihydropyrimidine-2-one was synthesized according to the reported procedure.…”

Section: Pyrimidine Ringmentioning

confidence: 99%

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2021

JPR

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The present work involves design, synthesis and evaluation of derivatives of 3,4-dihydropyrimidine 2 one. Using pyrimdine as a core structure for design of novel pyrimidine derivatives which are calcium channel blocker, Derivatives of 3,4-dihydropyrinidine-2-one was synthesized by microwave assisted synthesis method. There are ten derivatives are synthesized by microwave assisted synthesis in laboratory. The entire synthesized compound was tested using Insilco parameters like Pass online data, SwissADME parameters and toxicity parameters by using protox II. All the synthesized compound tested by pass online software for its biological activity. All the synthesized compounds reflelects various activities like antihypertensive, antianginal, antiviral, antifungal and all of them are calcium channel blockers.

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Perioperative acute hypertensionâ€”role of Clevidipine butyrate

Cited by 4 publications

References 49 publications

Synthesis, Docking Simulation, Biological Evaluations and 3D-QSAR Study of 1,4-Dihydropyridines as Calcium Channel Blockers

Synthesis, Docking Simulation, Biological Evaluations and 3D-QSAR Study of 1,4-Dihydropyridines as Calcium Channel Blockers

Adverse Cardiovascular Effects of Phenylephrine Eye Drops Combined With Intravenous Atropine

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