Page last updated: 2024-12-07

1,4-dihydropyridine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

1,4-Dihydropyridines (DHPs) are a class of heterocyclic compounds characterized by a six-membered ring containing one nitrogen atom and two double bonds. They are widely studied for their pharmacological activities, particularly as calcium channel blockers. DHPs can be synthesized through various methods, including the Hantzsch reaction, which involves the condensation of an aldehyde, two β-ketoesters, and ammonia. They exhibit a wide range of effects, including vasodilation, antihypertensive activity, anti-anginal effects, and neuroprotective properties. DHPs act by binding to and blocking L-type voltage-dependent calcium channels, which play a crucial role in regulating calcium influx into cells. Their ability to modulate calcium signaling makes them valuable therapeutic agents for treating cardiovascular disorders, such as hypertension, angina, and arrhythmias. Furthermore, DHPs are being explored for their potential therapeutic applications in other areas, including neurodegenerative diseases, diabetes, and cancer. The widespread interest in DHPs stems from their diverse pharmacological profiles, their established safety and efficacy, and their potential for further development into novel therapeutic agents.'

Cross-References

ID SourceID
PubMed CID104822
MeSH IDM0116612

Synonyms (12)

Synonym
pyridine,1,4-dihydro-
pyridine, 1,4-dihydro-
1,4-dihydropyridine
3337-17-5
pyridine, dihydro-
27790-75-6
AKOS006332198
7m8k3p6i89 ,
unii-7m8k3p6i89
DTXSID20274185
Q39094
4-dihydropyridine

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Efficacy outcomes of decrease in systolic (SBP) and diastolic (DBP) blood pressures from baseline, changes in heart rate (HR), and adverse effects were compared between dual CCB therapy vs."( Efficacy and safety of dual calcium channel blockade for the treatment of hypertension: a meta-analysis.
Alviar, CL; Bangalore, S; Benjo, AM; Devarapally, S; Doherty, B; Javed, F; Kang, H; Messerli, FH; Nadkarni, GN; Romero, J, 2013
)
0.39
" Dual CCB therapy did not increase adverse effects."( Efficacy and safety of dual calcium channel blockade for the treatment of hypertension: a meta-analysis.
Alviar, CL; Bangalore, S; Benjo, AM; Devarapally, S; Doherty, B; Javed, F; Kang, H; Messerli, FH; Nadkarni, GN; Romero, J, 2013
)
0.39
"Dual CCB therapy lowers blood pressure significantly better than CCB monotherapy, without an increase in adverse events."( Efficacy and safety of dual calcium channel blockade for the treatment of hypertension: a meta-analysis.
Alviar, CL; Bangalore, S; Benjo, AM; Devarapally, S; Doherty, B; Javed, F; Kang, H; Messerli, FH; Nadkarni, GN; Romero, J, 2013
)
0.39
" Treatment of cancer using the chemotherapeutic drugs have adverse side effects such as toxicity as they lose their specificity toward cancer cells and affect also normal cells."( Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and their Limited Side Effects on Normal Melanocytes.
Abdelhamid, IA; Elwahy, AHM; Ibrahim, NS; Mohamed, MF, 2018
)
0.75

Pharmacokinetics

ExcerptReferenceRelevance
"There was very little significant difference between SAMR1 and SAMP8 in terms of the half-life (t(1/2)), total body clearance (CL(tot)), steady-state volume of distribution (Vd(ss))."( In vivo specific binding characteristics and pharmacokinetics of a 1,4-dihydropyridine calcium channel antagonist in the senescent mouse brain.
Deguchi, Y; Kimura, R; Uchida, S; Yamada, S; Yamamoto, M, 2000
)
0.54
"A suitable, convenient and simple HPLC assay for pharmacokinetic study of mebudipine in rabbits was developed."( High performance liquid chromatography of mebudipine: application to pharmacokinetic study.
Bohlooli, S; Keyhanfar, F; Mahmoudian, M,
)
0.13
" Through, on the one hand, A beta peptide production measurements by specific in vitro assays (gamma-secretase Cell Free assay and Cell Based assay on HEK 293 APP transfected cells) and, on the other hand, pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent gamma-secretase inhibitory activity in vitro."( Substituted thiazolamide coupled to a redox delivery system: a new gamma-secretase inhibitor with enhanced pharmacokinetic profile.
Bihel, F; Garino, C; Kraus, JL; Laras, Y; Pietrancosta, N; Quéléver, G; Sheha, M; Wolfe, MS, 2005
)
0.33
" By using the above procedure, a simple, sensitive and convenient HPLC assay for determination, stability evaluation and pharmacokinetic study of nitrimidodipine was developed."( HPLC method for analysis of a new 1,4-dihydropyridine: application to pharmacokinetic study in rabbit.
Jamalian, A; Javidnia, K; Miri, R, 2006
)
0.61
" The pharmacokinetic interaction strengths were defined in common logarithmic values of increasing ratios of area under the plasma concentration-time curve (AUC) with GFJ intake compared with controls."( Relationship between lipophilicities of 1,4-dihydropyridine derivatives and pharmacokinetic interaction strengths with grapefruit juice.
Mohri, K; Uesawa, Y, 2008
)
0.61

Compound-Compound Interactions

ExcerptReferenceRelevance
" BB can be combined with vasodilators and alpha blockers with good therapeutic benefit."( Betablockers in combination with other antihypertensives.
Manjuran, RJ,
)
0.13

Bioavailability

ExcerptReferenceRelevance
" Oral bioavailability approached 100%, and hemodynamic responses were gradual in onset and long-lasting in effect."( Long-acting dihydropyridine calcium antagonists. 1. 2-Alkoxymethyl derivatives incorporating basic substituents.
Arrowsmith, JE; Blackburn, KJ; Burges, RA; Campbell, SF; Cross, PE; Gardiner, DG; Stubbs, JK, 1986
)
0.27
"05), mimicking the effect of an apparent decrease in bioavailability of endogenous NO."( Chronic nicotine alters NO signaling of Ca(2+) channels in cerebral arterioles.
Gerzanich, V; Simard, JM; West, GA; Zhang, F, 2001
)
0.31
" Agents that restore endothelial function and NO bioavailability have beneficial anti-atherogenic activities and can improve cardiovascular outcomes; this has been observed with angiotensin-converting enzyme (ACE) inhibitors, statins and certain dihydropyridine-type calcium channel blockers (CCBs)."( Atheroprotective effects of long-acting dihydropyridine-type calcium channel blockers: evidence from clinical trials and basic scientific research.
Mason, RP, 2003
)
0.32
" The influence of the Ca(2+) channel antagonists on pancreatic beta cell functions is dependent on lipophilicity, interactions with the cell membrane lipid bilayer, with SNAREs protein complexes in cell and vesicle membranes, with intracellular receptors, bioavailability and time of elimination from several organs and the bloodstream."( Effect of new and known 1,4-dihydropyridine derivatives on blood glucose levels in normal and streptozotocin-induced diabetic rats.
Bisenieks, E; Briede, J; Duburs, G; Makarova, N; Poikāns, J; Stivriņa, M; Stoldere, D; Uldriķis, J,
)
0.44
" Bioavailability studies revealed that both prodrugs 10 and 17 were rapidly cleared from blood with half lives of about 1 h, which will likely decrease systemic adverse effects."( Brain-specific delivery of naproxen using different carrier systems.
Mahmoud, S; Mohammad, A, 2010
)
0.36
"Amorphous materials are high-energy solids that can potentially enhance the bioavailability of poorly soluble compounds."( Trends in the precipitation and crystallization behavior of supersaturated aqueous solutions of poorly water-soluble drugs assessed using synchrotron radiation.
Alonzo, DE; Gao, Y; Mo, H; Raina, SA; Taylor, LS; Van Eerdenbrugh, B; Zhang, GGZ, 2015
)
0.42
" It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed."( Solid dispersions of efonidipine hydrochloride ethanolate with improved physicochemical and pharmacokinetic properties prepared with microwave treatment.
Fukami, T; Inoue, M; Maeno, Y; Otsuka, M; Ozeki, T; Tagami, T, 2016
)
0.43

Dosage Studied

ExcerptRelevanceReference
" Dose-response curves reveal that isradipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%."( Prevention of stroke and brain damage with calcium antagonists in animals.
Rudin, M; Sauter, A, 1991
)
0.28
" Dose-response curves to K+ show that following differentiation, cells become more sensitive, releasing transmitter at lower K+ concentrations."( Nerve growth factor modulates the drug sensitivity of neurotransmitter release from PC-12 cells.
Kongsamut, S; Miller, RJ, 1986
)
0.27
" In these animals, withdrawal of nimodipine for 48 hr returned the dose-response curve of sufentanil to the tolerant values, whereas Ca++ channels remained increased."( Regulation of dihydropyridine-sensitive Ca++ channels during opioid tolerance and supersensitivity in rats.
Díaz, A; Flórez, J; Hurlé, MA; Pazos, A; Ruíz, F, 1995
)
0.29
"We restricted the dose-response meta-analysis to the 16 randomized secondary-prevention trials of nifedipine for which mortality data were available."( Nifedipine. Dose-related increase in mortality in patients with coronary heart disease.
Furberg, CD; Meyer, JV; Psaty, BM, 1995
)
0.29
" dosing with DA-CDSac."( Synthesis and evaluation of a redox chemical delivery system for brain-enhanced dopamine containing an activated carbamate-type ester.
Bodor, N; Farag, HH; Omar, FA, 1994
)
0.29
" A total of 179 patients with a pretreatment mean baseline BP of 172 +/- 17/112 +/- 18 mm Hg enrolled in the trial and BP was recorded 24 h after dosing at baseline and weeks 2, 4, 8 and the final week (10-12 weeks)."( Losartan potassium as initial therapy in patients with severe hypertension.
Chrysant, S; Dunlay, MC; Fitzpatrick, V; Francischetti, EA; Goldberg, AI; Sweet, CS, 1995
)
0.29
" For both drug classes, we suggest that long-acting agents be considered, providing therapeutic coverage well beyond the normal dosing interval."( 1,4-Dihydropyridines versus beta-blockers for hypertension: are either safe for the heart?
Leenen, FH, 1996
)
1.74
" Nonetheless, although it appears paradoxical that agents which block the entry of Ca2+ into heart cells may be considered arrhythmogenic, there are circumstances under which dosage with certain calcium antagonists potentially leads to myocardial Ca2+ overload."( Are calcium antagonists proarrhythmic?
Bassett, AL; Chakko, S; Epstein, M, 1997
)
0.3
" Optimal use of these important drugs will involve careful dosing and sensitivity to strategies to diminish the likelihood of edema."( Incidence of pedal edema formation with dihydropyridine calcium channel blockers: issues and practical significance.
Weir, MR,
)
0.13
"8-fold difference in IC(50), but the slope of the dose-response curve was much steeper (n(H)=2."( Molecular mechanisms of vasoselectivity of the 1,4-dihydropyridine lercanidipine.
Herzig, S; Wirtz, S, 2004
)
0.58
" After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure."( Antiplatelet effect of clopidogrel can be reduced by calcium-channel blockers.
Kim, JY; Kim, YD; Lee, KY; Seo, KD; Yoon, YW, 2014
)
0.4
" These results can be a good opportunity to design new photoprotective pharmaceutical packaging for DHPs in liquid dosage form."( Photostabilization studies of antihypertensive 1,4-dihydropyridines using polymeric containers.
De Luca, M; Ioele, G; Ragno, G; Spatari, C, 2016
)
0.69
" This review article gives an overview of various analytical techniques proposed for the determination of LAC in pharmaceutical dosage forms, in pure form, in biological fluids and to determine characteristics of LAC in modified release dosage forms."( Lacidipine: review of analytical methods developed for pharmaceutical dosage forms and biological fluids.
Kumar, L; Sai Chebrolu, T; Verma, R, 2021
)
0.62
" In order to assess the pharmacokinetic parameters, toxicological properties and to estimate the exact concentration of LAC, various analytical techniques are employed for the estimation of LAC in pharmaceutical dosage forms, biological matrices and for the physical characterization of LAC."( Lacidipine: review of analytical methods developed for pharmaceutical dosage forms and biological fluids.
Kumar, L; Sai Chebrolu, T; Verma, R, 2021
)
0.62
" The widespread of PMS necessitate the development of an exceedingly sensitive and selective fluorimetric assay for its determination in pure form, different pharmaceutical dosage forms, and human plasma."( Selective Spectrofluorimetric Protocol for Determination of Commonly Used Gram-negative Bactericidal Drug in Combined Pharmaceutical Dosage Forms and Human Plasma.
Abdelmajed, MA; Attia, TZ; El-Din, KMB; Omar, MA, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (1,065)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990182 (17.09)18.7374
1990's384 (36.06)18.2507
2000's255 (23.94)29.6817
2010's210 (19.72)24.3611
2020's34 (3.19)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 38.10

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index38.10 (24.57)
Research Supply Index7.04 (2.92)
Research Growth Index4.63 (4.65)
Search Engine Demand Index57.69 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (38.10)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials23 (2.06%)5.53%
Reviews87 (7.80%)6.00%
Case Studies7 (0.63%)4.05%
Observational0 (0.00%)0.25%
Other998 (89.51%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (3)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Effects of Dihydropyridine Calcium Channel Inhibitors on Respiratory Gas Exchanges in the Intensive Care Unit: a Pharmacovigilance Study in VigiBase® and a Comparison With Urapidil [NCT05537194]32,000,000 participants (Actual)Observational1963-01-01Completed
Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM)- Dihydropyridine Calcium Channel Blockers Versus Hydrochlorothiazide [NCT05125224]163,720 participants (Actual)Observational2021-10-01Active, not recruiting
Replication of the TRANSCEND Antihypertensive Trial in Healthcare Claims Data [NCT04354376]40,048 participants (Actual)Observational2017-09-22Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]