Amlodipine chemical structure (dihydropyridine CCB), 2D skeletal formula, C20H25ClN2O5

Amlodipine Chemical Structure

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1. Identification

Summary

Amlodipine is a dihydropyridine calcium-channel blocker for hypertension and chronic stable/vasospastic angina; long half-life supports once-daily dosing.

Brand Names

Norvasc; multiple generics

Name

Amlodipine

Background

Racemic, lipophilic dihydropyridine; marketed clinically as amlodipine besylate; oral tablets and solutions dominate.

Modality

Small molecule

Groups

Approved; prescription

Structure

Amlodipine 2D chemical structure (dihydropyridine). Formula C20H25ClN2O5; IUPAC long name; CAS 88150-42-9.
Amlodipine chemical structure (dihydropyridine CCB), 2D skeletal formula, C20H25ClN2O5

Weight

≈ 408.88 g/mol (free base)

Chemical Formula

C₂₀H₂₅ClN₂O₅ (free base)

Synonyms

(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

External IDs

CAS (base): 88150-42-9; PubChem CID: 2162; UNII (base): 1J444QC288; ATC: C08CA01

2. Pharmacology

Indication

Hypertension; chronic stable angina; vasospastic (Prinzmetal) angina.

Associated Conditions

CAD without heart failure; pediatric hypertension (≥6 years) per labels.

Associated Therapies

Fixed combinations with ARBs/ACEIs; co-therapy with statins and other antihypertensives as needed.

Contraindications & Blackbox Warnings

No boxed warning; contraindicated in known hypersensitivity. Dose cautiously in hepatic impairment.

Pharmacodynamics

Selective L-type Ca²⁺ channel blockade in vascular smooth muscle → arteriolar vasodilation → ↓ SVR and BP; minimal direct cardiac suppression at therapeutic dose.

Mechanism of action

Dihydropyridine ring binds L-type channels in the inactivated state, reducing Ca²⁺ influx and tone.

Absorption

Oral bioavailability ~64–90%; tₘₐₓ 6–12 h; food does not meaningfully alter exposure.

Volume of distribution

~21 L/kg (large, extensive tissue distribution).

Protein binding

~93–98%.

Metabolism

Extensive hepatic metabolism (primarily CYP3A4) to inactive metabolites.

Route of elimination

~60% of dose recovered in urine as metabolites; ~10% unchanged; fecal remainder.

Half-life

~30–50 h (longer in hepatic impairment).

Clearance

Hepatic; exposure increases with strong CYP3A inhibition.

Adverse Effects

Peripheral edema, dizziness, flushing, palpitations; uncommon hypotension; rare serious hepatic or dermatologic events.

Toxicity

Overdose → profound vasodilation and hypotension; supportive care and vasopressors as indicated.

Pathways

Calcium influx inhibition (L-type); hemodynamic afterload reduction.

Pharmacogenomic Effects/ADRs

No routine PGx; transporter/enzyme variants (e.g., CYP3A, CYP3A5) may modulate exposure.

3. Interactions

Drug Interactions

Strong CYP3A inhibitors (e.g., clarithromycin, azoles, protease inhibitors) ↑ amlodipine levels; monitor dose. Simvastatin exposure increases—limit simvastatin to ≤20 mg/day when co-administered. Minimal effect on binding of digoxin/warfarin/phenytoin/indomethacin in vitro.

Food Interactions

Food: no relevant effect. Grapefruit juice: no significant effect on amlodipine PK at tested amounts.

4. Categories

ATC Codes

C08CA01 (amlodipine, dihydropyridine derivatives)

Drug Categories

Calcium-channel blocker; Antihypertensive; Antianginal; Small molecule

Chemical Taxonomy

1,4-dihydropyridine with 2-chlorophenyl substituent; diester at 3,5-positions; tertiary amine side chain.

Affected organisms

Humans (therapeutic use)

5. Chemical Identifiers

UNII

1J444QC288 (amlodipine, base)

CAS number

88150-42-9 (base)

InChI Key

HTIQEAQVCYTUBX-UHFFFAOYSA-N

InChI

InChI=1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3

IUPAC Name

(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

SMILES

Clc1ccccc1C2/C(C(=O)OC)=C(/C)N/C(COCCN)=C2/C(=O)OCC

6. References

DailyMed/Norvasc labels: bioavailability 64–90%; tₘₐₓ 6–12 h; protein binding ~93%; renal recovery 10% unchanged; half-life 30–50 h; grapefruit juice no significant effect. DailyMed+4DailyMed+4DailyMed+4
Pfizer Norvasc label PDF: Vd ≈21 L/kg; protein binding ≈97.5%; food no effect. Pfizer Labeling
Clinical PK literature: Vd ~21 L/kg; high protein binding ~98%; clearance values in adults. FDA Access Data+3PubMed+3SpringerLink+3
PubChem: identifiers (CID 2162), formula C₂₀H₂₅ClN₂O₅, canonical InChI/SMILES. PubChem
CAS Common Chemistry: CAS 88150-42-9; InChIKey HTIQEAQVCYTUBX-UHFFFAOYSA-N. Common Chemistry
FDA GSRS/UNII: 1J444QC288; formula; InChIKey. precisionFDA
WHOCC ATC/DDD Index: C08CA01 classification. FHI

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