QuickView for Felodipine (compound)

Summary
General Info

PubChem

PubChem Compound 3333

Name:	Felodipine
PubChem Compound ID:	3333
Description:	A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.
Molecular formula:	C₁₈H₁₉Cl₂NO₄
Molecular weight:	384.253 g/mol
Synonyms:	Felodipinum [INN-Latin]; Flodil; Perfudal; H 154/82; H-154/82; D00319; Hydac; BRN 4331472; MLS000069629; Felodipine. show more » Felodipinum [INN-Latin]; Flodil; Perfudal; H 154/82; H-154/82; D00319; Hydac; BRN 4331472; MLS000069629; Felodipine; 3,5-pyridinedicarboxylic acid, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-, ethyl methyl ester; Plendil; dl-Felodipine; Renedil; Felodipina [INN-Spanish]; Lexxel; Prestwick1_000478; Agon; Prevex; SPBio_002555; AGON SR; Preslow; LS-131202; Splendil; 3,5-Pyridinedicarboxylic acid, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-, ethyl methyl ester, (+-)-; 72509-76-3; Feloday; Munobal; Felodipine (JAN/USP); Felogard; Prestwick_797; (+-)-Ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate; Felodipine [USAN:BAN:INN]; Plendil Retard; Logimax; Plendil ER; Plendil (TN); EU-0100508; CGH-869; 86189-69-7; 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-4-(2,3-dichlorophenyl)-2,6-dimethyl-, ethyl methyl ester; AE-641/11429675; Penedil; Munobal Retard; SMR000058204; Modip; Plendil Depottab; Prestwick0_000478; Felodur ER show less «

DrugBank

Identification

Name:	Felodipine
Name (isomeric):	DB01023
Drug Type:	small molecule
Description:	A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.
Synonyms:	Felodipinum [INN-Latin]; Dl-Felodipine; Felodipina [INN-Spanish]; Felodipine [Usan:Ban:Inn]
Brand:	Plendil ER, Hydac, AGON SR, Feloday, Felodur ER, Perfudal, Plendil, Flodil, Modip, Lexxel, Penedil, Plendil Depottab, Munobal, Felogard, Splendil, Renedil, Preslow, Munobal Retard, Plendil Retard, Agon, Plandil, Prevex
Brand name mixture:	Lexxel(felodipine + enalapril maleate)
Category:	Vasodilator Agents, Calcium Channel Blockers, Antihypertensive Agents, Dihydropyridines
CAS number:	72509-76-3

Pharmacology

Indication:	For the treatment of mild to moderate essential hypertension.
Pharmacology:	Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contr... show more » Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells. show less «
Mechanism of Action:	Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the c... show more » Felodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Felodipine may be used to treat mild to moderate essential hypertension. show less «
Absorption:	Is completely absorbed from the gastrointestinal tract; however, extensive first-pass metabolism through the portal circulation results in a low systemic availability of 15%. Bioavailability is unaffected by food.
Protein binding:	99%, primarily to the albumin fraction.
Biotransformation:	Hepatic metabolism primarily via cytochrome P450 3A4. Six metabolites with no appreciable vasodilatory effects have been identified.
Route of elimination:	Although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.
Half Life:	17.5-31.5 hours in hypertensive patients; 19.1-35.9 hours in elderly hypertensive patients; 8.5-19.7 in healthy volunteers.
Clearance:	0.8 L/min [Young healthy subjects]
Toxicity:	Symptoms of overdose include excessive peripheral vasodilation with marked hypotension and possibly bradycardia. Oral rat LD₅₀ is 1050 mg/kg.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take without regard to meals.

Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nifedipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of nifedipine and may cause toxicity. Avoid grapefruit products while on this medication.

Drug interaction:

Methylphenobarbital	The barbiturate, methylphenobarbital, decreases the effect of felodipine.
Nelfinavir	Nelfinavir increases the effect and toxicity of felodipine
Dihydroquinidine barbiturate	The barbiturate, dihydroquinidine barbiturate, decreases the effect of felodipine.
Secobarbital	The barbiturate, secobarbital, decreases the effect of felodipine.
Oxcarbazepine	Oxcarbazepine decreases the levels of felodipine

Methylphenobarbital	The barbiturate, methylphenobarbital, decreases the effect of felodipine.
Nelfinavir	Nelfinavir increases the effect and toxicity of felodipine
Dihydroquinidine barbiturate	The barbiturate, dihydroquinidine barbiturate, decreases the effect of felodipine.
Secobarbital	The barbiturate, secobarbital, decreases the effect of felodipine.
Oxcarbazepine	Oxcarbazepine decreases the levels of felodipine
Pentobarbital	The barbiturate, pentobarbital, decreases the effect of felodipine.
Erythromycin	Erythromycin increases the effect of felodipine
Heptabarbital	The barbiturate, heptabarbital, decreases the effect of felodipine.
Amobarbital	The barbiturate, amobarbital, decreases the effect of felodipine.
Tacrolimus	Felodipine increases tacrolimus levels
Josamycin	Erythromycin increases the effect of felodipine
Telithromycin	Telithromycin may reduce clearance of Felodipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Felodipine if Telithromycin is initiated, discontinued or dose changed.
Butabarbital	The barbiturate, butabarbital, decreases the effect of felodipine.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of felodipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of felodipine if voriconazole is initiated, discontinued or dose changed.
Thiopental	The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Felodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Felodipine if Thiopental is initiated, discontinued or dose changed.
Tretinoin	The moderate CYP2C8 inhibitor, Felopidine, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Felopidine is initiated, discontinued to dose changed.
Treprostinil	Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Talbutal	The barbiturate, talbutal, decreases the effect of felodipine.
Primidone	The barbiturate, primidone, decreases the effect of felodipine.
Butalbital	The barbiturate, butalbital, decreases the effect of felodipine.
Hexobarbital	The barbiturate, hexobarbital, decreases the effect of felodipine.
Fosphenytoin	The hydantoin decreases the effect of felodipine
Carbamazepine	Carbamazepine may increase the metabolism of felodipine. Monitor for changes in the therapeutic and adverse effects of felodipine if carbamazepine is initiated, discontinued or dose changed.
Phenytoin	The hydantoin decreases the effect of felodipine
Ethotoin	The hydantoin decreases the effect of felodipine
Mephenytoin	The hydantoin decreases the effect of felodipine
Aprobarbital	The barbiturate, aprobarbital, decreases the effect of felodipine.
Quinupristin	This combination presents an increased risk of toxicity
Itraconazole	Itraconazole may increase the therapeutic and adverse effects of felodipine.
Methohexital	The barbiturate, methohexital, decreases the effect of felodipine.
Quinidine barbiturate	The barbiturate, quinidine barbiturate, decreases the effect of felodipine.
Phenobarbital	The barbiturate, phenobarbital, decreases the effect of felodipine.
Tipranavir	Tipranavir, co-administered with Ritonavir, may alter the concentration of Felopidine. Monitor for efficacy and adverse/toxic effects of Felopidine.
Butethal	The barbiturate, butethal, decreases the effect of felodipine.