Manidipine

Identification

Name

Manidipine

Accession Number

DB09238

Description

Manidipine (INN) is a calcium channel blocker (dihydropyridine type) that is used clinically as an antihypertensive. It is selective for vasculature and does not produce effects on the heart at clinically relevant dosages.

Type

Small Molecule

Groups

Approved, Investigational

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Manidipine (DB09238)

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Weight

Average: 610.711
Monoisotopic: 610.27913496

Chemical Formula

C₃₅H₃₈N₄O₆

Synonyms

• Manidipine
• Manidipino

Pharmacology

Indication

For the treatment of hypertension.

Associated Conditions

• Mild to Moderate Hypertension

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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Pharmacodynamics

Manidipine produces vasodilation resulting in lower blood pressure ¹.

Mechanism of action

Contraction of vascular smooth muscle is stimulated by Gq coupled receptors which produce calcium release from the sarcoplasmic reticulum. This is followed by opening of voltage dependent calcium channels and an influx of calcium into the cell ultimately producing contraction. Manidipine binds to and dissociates slowly from L- and T-type voltage dependent calcium channels on smooth muscle cells, blocking the entrance of extracellular calcium into the cell and preventing this contraction ^1,2. This produces vasodilation which decreases blood pressure. Manidipine produces renal vasodilation and an increase in natriuresis. This likely contributes to the antihypertensive effect by reducing blood volume. Manidipine is selective for the vasculature and does not produce significant effects on the heart or central nervous system at clinically relevant dosages.

Target	Actions	Organism
AVoltage-dependent L-type calcium channel	blocker	Humans
AVoltage-dependent T-type calcium channel	blocker	Humans

Absorption

The median Tmax is 1.5 h ¹. Administration with food produces an 1.3-1.6-fold increase in Cmax but no change in Tmax. Manidipine does not accumulate significantly with multiple doses.

Volume of distribution

Not Available

Protein binding

Manidipine is 99% bound to human plasma proteins ¹.

Metabolism

Manidipine is extensively metabolized by CYP enzymes to pyridine derivatives and diphenylmethane derivatives which make up 4-7% and 22-24% of the dose excreted in the urine ¹.

Route of elimination

Manidipine is eliminated through extensive metabolism. 63% is eliminated in the feces and 31% in the urine as metabolites ¹.

Half-life

The half life of elimination has been observed to be dose dependent ¹. Doses of 5, 10, and 20 mg produced half lives of 3.94, 5.02, and 7.95 h respectively.

Clearance

Not Available

Adverse Effects

Learn about our commercial Adverse Effects data.

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Toxicity

The most common adverse events reported in clinical trials were ankle oedema (6%), headache (3.8%), palpitation (2.7%), flushing (2.2%), dizziness (1.6%), rash (0.5%) and fatigue (0.5%) ¹.

Affected organisms

• Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abametapir	The serum concentration of Manidipine can be increased when it is combined with Abametapir.
Abemaciclib	The metabolism of Abemaciclib can be decreased when combined with Manidipine.
Acalabrutinib	The metabolism of Acalabrutinib can be decreased when combined with Manidipine.
Acarbose	The risk or severity of hypoglycemia can be increased when Manidipine is combined with Acarbose.
Acebutolol	The metabolism of Acebutolol can be decreased when combined with Manidipine.
Aceclofenac	The therapeutic efficacy of Manidipine can be decreased when used in combination with Aceclofenac.
Acemetacin	The therapeutic efficacy of Manidipine can be decreased when used in combination with Acemetacin.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Manidipine.
Acetaminophen	The metabolism of Manidipine can be decreased when combined with Acetaminophen.
Acetohexamide	The metabolism of Acetohexamide can be decreased when combined with Manidipine.

Additional Data Available

Extended Description
Extended Description
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Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
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A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
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Action
Action
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Food Interactions

Not Available

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Manidipine dihydrochloride	ZL507UZ6QL	89226-75-5	JINNGBXKBDUGQT-UHFFFAOYSA-N

International/Other Brands

Manyper

Categories

ATC Codes

C08CA11 — Manidipine

• C08CA — Dihydropyridine derivatives
• C08C — SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS
• C08 — CALCIUM CHANNEL BLOCKERS
• C — CARDIOVASCULAR SYSTEM

C09BB12 — Delapril and manidipine

• C09BB — ACE inhibitors and calcium channel blockers
• C09B — ACE INHIBITORS, COMBINATIONS
• C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
• C — CARDIOVASCULAR SYSTEM

Drug Categories

• ACE Inhibitors and Calcium Channel Blockers
• Agents causing hyperkalemia
• Antiarrhythmic agents
• Antihypertensive Agents
• Bradycardia-Causing Agents
• Calcium Channel Blockers
• Calcium-Regulating Hormones and Agents
• Cardiovascular Agents
• Cytochrome P-450 CYP2B6 Inhibitors
• Cytochrome P-450 CYP2B6 Inhibitors (weak)
• Cytochrome P-450 CYP2C19 Inhibitors
• Cytochrome P-450 CYP2C19 Inhibitors (weak)
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2D6 Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors (moderate)
• Cytochrome P-450 CYP2D6 Inhibitors (weak)
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (weak)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Dihydropyridine Derivatives
• Membrane Transport Modulators
• Pyridines
• Selective Calcium Channel Blockers With Mainly Vascular Effects
• Vasodilating Agents

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Diphenylmethanes

Direct Parent

Diphenylmethanes

Alternative Parents

Dihydropyridinecarboxylic acids and derivatives / Nitrobenzenes / Nitroaromatic compounds / Aralkylamines / N-alkylpiperazines / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Methyl esters / Amino acids and derivatives / Trialkylamines / Azacyclic compounds / Enamines / Propargyl-type 1,3-dipolar organic compounds / Dialkylamines / Organic oxoazanium compounds / Organopnictogen compounds / Hydrocarbon derivatives / Carbonyl compounds / Organic zwitterions / Organic oxides

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Substituents

1,4-diazinane / Allyl-type 1,3-dipolar organic compound / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / C-nitro compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dicarboxylic acid or derivatives / Dihydropyridine / Dihydropyridinecarboxylic acid derivative / Diphenylmethane / Enamine / Enoate ester / Hydrocarbon derivative / Hydropyridine / Methyl ester / N-alkylpiperazine / Nitroaromatic compound / Nitrobenzene / Organic 1,3-dipolar compound / Organic nitro compound / Organic nitrogen compound / Organic oxide / Organic oxoazanium / Organic oxygen compound / Organic zwitterion / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Piperazine / Propargyl-type 1,3-dipolar organic compound / Secondary aliphatic amine / Secondary amine / Tertiary aliphatic amine / Tertiary amine / Vinylogous amide

show 32 more

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

Not Available

Chemical Identifiers

UNII

6O4754US88

CAS number

89226-50-6

InChI Key

ANEBWFXPVPTEET-UHFFFAOYSA-N

InChI

InChI=1S/C35H38N4O6/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-16,23,32-33,36H,17-22H2,1-3H3

IUPAC Name

3-{2-[4-(diphenylmethyl)piperazin-1-yl]ethyl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

SMILES

COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)N(=O)=O)C(=O)OCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1

References

General References

1. Cheer SM, McClellan K: Manidipine: a review of its use in hypertension. Drugs. 2001;61(12):1777-99. [PubMed:11693466]
2. McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [PubMed:15329044]

External Links

PubChem Compound

4008

PubChem Substance

347827830

ChemSpider

3868

RxNav

29275

ChEBI

135849

ChEMBL

CHEMBL1085699

Wikipedia

Manidipine

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Cardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Stroke	1
4	Terminated	Treatment	High Blood Pressure (Hypertension)	1
3	Completed	Diagnostic	Type 2 Diabetes Mellitus	1
3	Completed	Treatment	High Blood Pressure (Hypertension)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	10 MG
Tablet	Oral	20 MG
Tablet	Oral	30 mg

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	<1mg/mL	MSDS

Predicted Properties

Property	Value	Source
Water Solubility	0.000995 mg/mL	ALOGPS
logP	5.11	ALOGPS
logP	5.19	ChemAxon
logS	-5.8	ALOGPS
pKa (Strongest Acidic)	19.47	ChemAxon
pKa (Strongest Basic)	7.89	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	7	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	116.93 Å2	ChemAxon
Rotatable Bond Count	12	ChemAxon
Refractivity	175.13 m3·mol-1	ChemAxon
Polarizability	65.72 Å3	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

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Drug created on October 23, 2015 10:51 / Updated on January 20, 2021 00:45