Advertisement

Topics

Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine.

08:00 EDT 6th April 2019 | BioPortfolio

Summary of "Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine."

The inhibitory effects of antihypertensive drugs (dihydropyridine calcium channel blockers, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors) on cytochrome P450 2J2 (CYP2J2) activity were examined. Amlodipine, azelnidipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nisoldipine, nitrendipine, telmisartan, delapril, and quinapril inhibited luciferin-2J2/4F12 O-dealkylase activity of recombinant human CYP2J2 in a concentration-dependent manner (IC = 0.116-9.19 μM). Kinetic analyses of the inhibition indicated that azelnidipine, barnidipine, benidipine, cilnidipine, efonidipine, manidipine, nicardipine, telmisartan, delapril, and quinapril competitively inhibited CYP2J2 activity, while amlodipine, felodipine, nifedipine, nilvadipine, nisoldipine, and nitrendipine showed mixed inhibition. Among these drugs, manidipine showed the strongest reversible inhibition with K value of 0.0294 μM. The docking simulation data supported the potent inhibition of CYP2J2 by these drugs. Next, the effect of preincubation on CYP2J2 inhibition was investigated to determine whether these antihypertensive drugs inhibited CYP2J2 activity in a metabolism-dependent manner. A 20-min preincubation of azelnidipine and felodipine in the presence of NADPH potentiated the inhibition of CYP2J2. Furthermore, kinetic analysis of the inactivation showed that azelnidipine caused a preincubation time- and concentration-dependent decrease in CYP2J2 activity yielding k/K value of 105 l/mmol/min, although felodipine showed no preincubation time-dependent inhibition. The azelnidipine-mediated inactivation required NADPH. These results indicated that manidipine is a potent competitive reversible inhibitor while azelnidipine is a potent mechanism-based inactivator of human CYP2J2.

Affiliation

Journal Details

This article was published in the following journal.

Name: Chemico-biological interactions
ISSN: 1872-7786
Pages:

Links

DeepDyve research library

PubMed Articles [36092 Associated PubMed Articles listed on BioPortfolio]

Effects of catalpol on the activity of human liver cytochrome P450 enzymes.

1. Catalpol possesses numerous pharmacological activities, and however, little data available for the effects of catalpol on the activity of human liver cytochrome P450 (CYP) enzymes. 2. This study in...

Inhibitory Mechanisms of Myricetin on Human and Rat Liver Cytochrome P450 Enzymes.

Myricetin is a flavonoid compound that is abundant in teas, red wine, berries, herbs and vegetables with a variety of pharmacological properties such as antioxidant, anti-inflammatory and anti-cancer ...

Mechanism-based inactivation of cytochrome P450 2D6 by chelidonine.

Chelidonine (CHE) is a major bioactive constituent of greater celandine, a plant used in traditional herbal medicines. CHE has widely been used as an analgesic in clinical settings. We evaluated the i...

From electrochemistry to enzyme kinetics of cytochrome P450.

This review is an attempt to describe advancements in the electrochemistry of cytochrome P450 enzymes (EC 1.14.14.1) and to study molecular aspects and catalytic behavior of enzymatic electrocatalysis...

Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro.

The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in term...

Clinical Trials [11858 Associated Clinical Trials listed on BioPortfolio]

The Impact of Cytochrome P450 Abnormalities in Patients With Delirium.

Objectives: 1. To examine whether patients with delirium have higher prevalence of cytochrome-P450 abnormalities compared to patients without delirium. 2. To examine wheth...

Polymorphic Effects of Cytochrome P450 3A5 on Pharmacokinetics of Maraviroc and Its Metabolites

The purpose of this study is to evaluate the influence of genetic polymorphism of cytochrome P450 3A5 on pharmacokinetics of maraviroc and its oxidative metabolites

A Study to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple Probe Substrate Cocktail in Healthy Subjects

The main purpose of this study is to determine the potential inhibitory/inducing effects of JNJ-54175446 after single and repeated dosing on the single-dose pharmacokinetics (PK) of a cock...

Drug Interaction Study Between AZD3480 and Cytochrome P450

The purpose of the study is to evaluate if AZD3480 inhibits Cytochrome P450 1A2, 2C19, 3A4, 2C8, 2B6 and UGT1A1 activity.

An Open-label Drug-Drug Interaction Study to Evaluate the Effect of BCX7353 on Cytochrome P450 Enzyme Activity Using Probe Substrates

This is an open-label, single sequence study to evaluate the effect of BCX7353 on hepatic and intestinal cytochrome P450 enzymes using probe substrate drugs in healthy subjects. Pharmacoki...

Medical and Biotech [MESH] Definitions

A cytochrome P450 enzyme family that includes members with critical functions in the metabolism of drugs and SEX HORMONES.

A cytochrome P450 enzyme family whose members function primarily in the metabolism of XENOBIOTICS, including drugs and POLYCYCLIC AROMATIC HYDROCARBONS.

A cytochrome P450 enzyme family whose members function in VITAMIN D metabolism and the biosynthesis of BILE ACIDS.

A cytochrome P450 enzyme family that includes members which function in the metabolism of STEROIDS; COUMARINS; and NICOTINE.

A cytochrome P450 enzyme family that functions in the biosynthesis of STEROIDS and includes STEROID 17-ALPHA-HYDROXYLASE.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Recombinant DNA
Recombinant DNA is the formation of a novel DNA sequence by the formation of two DNA strands. These are taken from two different organisms. These recombinant DNA molecules can be made with recombinant DNA technology. The procedure is to cut the DNA of ...


Searches Linking to this Article