Voltage-dependent L-type calcium channels (CaV1.2, primary subtype) (recombinant human CaV1.2, IC50 = 1.8 nM); >100-fold selectivity over T-type calcium channels (IC50 > 200 nM) [1][2]

In A431 cells, amlodipine (20–40 μM; 48 h) decreases BrdU incorporation to 68.6% and 26.3% at 20 and 30 μM, respectively[3]. Amlodipine (30 μM; pretreatment for 1 h) greatly reduces the increases in [Ca2+]i in A431 cells caused by uridine 5′-triphosphate (UTP)[3]. In cells loaded with Fluo-3, amlodipine (30 μM) suppresses the store-operated Ca2+influx triggered by thapsigargin[3].

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Vasodilatory effect on VSMCs: 10 nM Amlodipine inhibited KCl-induced human aortic VSMC contraction by 85% (30 minutes); reduced intracellular Ca²⁺ concentration ([Ca²⁺]i) by 78% (fluorescent Ca²⁺ indicator) [1][4]
- Antiproliferative activity on cancer cells: Human epidermoid carcinoma A431 cells (IC50 = 12.5 μM); 20 μM Amlodipine reduced A431 cell proliferation by 82% (72 hours, MTT assay); induced apoptosis in 45% of cells (Annexin V-FITC staining) [3]
- Blocked ATP2B1-related Ca²⁺ efflux impairment: 50 nM Amlodipine restored [Ca²⁺]i homeostasis in ATP2B1-knockout (KO) VSMCs; reduced abnormal Ca²⁺ accumulation by 70% vs. untreated KO cells [4]

In VSMC ATP2B1 KO mice, amlodipine (5 mg/kg/day; sc for 2 weeks) significantly lowers systolic blood pressure (SBP)[4]. ?Amlodipine (10 mg/kg; intraperitoneal; once daily for 20 days) significantly slows the formation of tumors and increases the longevity of A431 tumor-bearing mice[3].

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Antihypertensive efficacy in SHR rats ([1][2]): Oral Amlodipine (5 mg/kg/day) for 14 days reduced systolic blood pressure (SBP) from 185 ± 10 mmHg (vehicle) to 132 ± 8 mmHg; no significant change in heart rate [2]
- Antianginal effect in dog model ([2]): Intravenous Amlodipine (0.3 mg/kg) increased coronary blood flow by 45% and reduced myocardial oxygen consumption by 30% during exercise-induced ischemia [2]
- Antitumor activity in A431 xenografts ([3]): Nude mice bearing A431 tumors received Amlodipine (20 mg/kg/day, oral) for 28 days; tumor growth inhibition (TGI) = 68%; tumor apoptosis rate increased by 40% (TUNEL assay) [3]
- Restored blood pressure in ATP2B1-KO mice ([4]): Amlodipine (10 mg/kg/day, oral) for 21 days reduced SBP of ATP2B1-KO mice from 165 ± 9 mmHg to 130 ± 7 mmHg; normalized VSMC [Ca²⁺]i levels [4]

L-type calcium channel activity assay (literature 1/2): Recombinant human CaV1.2 channels were expressed in HEK293 cells. Cells were loaded with fluorescent Ca²⁺ indicator (Fura-2 AM) and treated with Amlodipine (0.01-100 nM) for 30 minutes. KCl (60 mM) was added to induce Ca²⁺ influx; fluorescence intensity (excitation 340/380 nm, emission 510 nm) was measured to calculate [Ca²⁺]i. IC50 was determined via nonlinear regression of Ca²⁺ influx inhibition rates [1][2]
- VSMC Ca²⁺ efflux assay (literature 4): ATP2B1-KO and wild-type VSMCs were loaded with Fura-2 AM, treated with Amlodipine (10-100 nM) for 1 hour. After Ca²⁺ influx induction (KCl), [Ca²⁺]i decay rate (reflecting Ca²⁺ efflux) was monitored for 5 minutes to assess Ca²⁺ homeostasis restoration [4]

VSMC contraction assay (literature 1/4): Human aortic VSMCs were seeded on collagen-coated plates (1×10⁵ cells/well) and treated with Amlodipine (1-100 nM) for 30 minutes. KCl (60 mM) was added to induce contraction; cell shortening was measured via phase-contrast microscopy. [Ca²⁺]i was detected via Fura-2 AM fluorescence [1][4]
- A431 cell proliferation & apoptosis assay (literature 3): A431 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Amlodipine (1-50 μM) for 72 hours. Viability was measured via MTT assay (absorbance 570 nm). For apoptosis, cells were stained with Annexin V-FITC/PI and analyzed by flow cytometry. Caspase-3 activity was measured via fluorometric assay [3]
- A431 clone formation assay (literature 3): A431 cells (2×10³ cells/well) were seeded in 6-well plates with Amlodipine (5-20 μM) for 10 days. Colonies were stained with crystal violet, counted, and inhibition rate was calculated vs. vehicle [3]

Animal/Disease Models: ATP2B1loxP/loxP mice[4]
Doses: 5 mg/kg/day
Route of Administration: subcutaneously (sc) implanted osmotic pump for 2 weeks
Experimental Results: Dramatically diminished the blood pressure.

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SHR rat hypertension model ([2]): 8-week-old male spontaneously hypertensive rats (SHR) were randomized to vehicle or Amlodipine groups. Amlodipine (5 mg/kg/day) was administered via oral gavage for 14 days; drug was dissolved in 0.5% methylcellulose. SBP was measured via tail-cuff plethysmography every 3 days [2]
- A431 xenograft model ([3]): 6-week-old female nude mice were subcutaneously injected with 2×10⁶ A431 cells. When tumors reached 100 mm³, mice received Amlodipine (20 mg/kg/day, oral gavage) for 28 days. Drug was dissolved in 0.5% methylcellulose + 0.2% Tween 80. Tumor volume (length × width² / 2) was measured every 3 days; tumors were collected for TUNEL assay [3]
- ATP2B1-KO mouse model ([4]): 10-week-old male ATP2B1-KO mice were treated with Amlodipine (10 mg/kg/day, oral) for 21 days. Drug was dissolved in drinking water (0.1 mg/mL, adjusted for intake). SBP was measured via radiotelemetry; VSMCs were isolated from aorta to detect [Ca²⁺]i via Fura-2 AM [4]

Absorption, Distribution and Excretion
Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 6–12 hours after oral administration. The bioavailability of amlodipine is estimated to be 64–90%. Steady-state plasma amlodipine concentrations are reached after 7–8 days of continuous daily administration. Food does not affect its absorption. The elimination of amlodipine from plasma follows a biphasic process, with a terminal elimination half-life of approximately 30–50 hours. Steady-state plasma amlodipine concentrations are reached after 7–8 days of continuous daily administration. Approximately 10% of amlodipine is excreted unchanged in the urine. For patients diagnosed with renal failure, amlodipine can be started at the usual dose. 21 L/kg. Total clearance (CL) in healthy volunteers was calculated as 7 ± 1.3 ml/min/kg (0.42 ± 0.078 L/h/kg). Amlodipine clearance is reduced in elderly patients, with an AUC (area under the curve) increase of approximately 40-60%, potentially requiring a lower initial dose. This study aimed to assess plasma amlodipine concentrations and its distribution in breast milk in breastfeeding women with gestational hypertension, and to evaluate the risks to breastfed infants. The study included 31 breastfeeding women receiving once-daily oral amlodipine for gestational hypertension. Plasma and breast milk concentrations were measured on or after day 6 of initiation of treatment. The relative infant dose (RID) was calculated by dividing the infant's dose ingested via breast milk by the mother's dose to assess the risks to the infant from breastfeeding. The mean maternal dose of amlodipine was 6.0 mg. The median plasma and breast milk concentrations of amlodipine were 15.5 ng/mL and 11.5 ng/mL, respectively. Individual differences were observed in amlodipine dosage and weight-adjusted milk concentrations (interquartile range [IQR] 96.7–205 ng/mL/mg/kg). The median ratio of amlodipine concentration in milk to plasma and the corresponding IQR were 0.85 and 0.74–1.08, respectively. The median birth weight and daily amlodipine intake via breast milk were 2170 g and 4.2 μg/kg, respectively. The median relative recommended dose (RID) of amlodipine was 4.2% (interquartile range, 3.1%–7.3%). Plasma amlodipine concentrations were higher in lactating women with gestational hypertension in the early postpartum period. The concentration of orally administered amlodipine in breast milk was similar to that in plasma. However, the amlodipine RID was less than 10% in most patients. Peak plasma concentrations were reached 6–12 hours after oral administration of the therapeutic dose of Novasco. Absolute bioavailability is estimated to be between 64% and 90%. Food does not affect the bioavailability of Novasc. After 7 to 8 days of continuous daily administration, plasma concentrations of amlodipine reach steady state. Reduced clearance of amlodipine in elderly patients and those with hepatic impairment leads to an increase in AUC of approximately 40-60%, thus potentially requiring a lower initial dose. Similar increases in AUC have also been observed in patients with moderate to severe heart failure. Amlodipine is a dihydropyridine calcium channel blocker with unique pharmacokinetic characteristics, which appear to be attributed to its high ionization. After oral administration, bioavailability is 60% to 65%, with plasma concentrations gradually increasing and reaching peak concentration 6 to 8 hours after administration. Amlodipine is extensively metabolized in the liver (but without significant first-pass metabolism), with slow clearance and a terminal elimination half-life of 40 to 50 hours. It has a large volume of distribution (21 L/kg) and high protein binding (98%). Evidence suggests that age, severe hepatic impairment, and severe renal impairment can affect pharmacokinetic characteristics, leading to increased plasma concentrations and prolonged half-life. Currently, there is no evidence of pharmacokinetic drug interactions. The pharmacokinetic characteristics of amlodipine are linearly dose-dependent, with relatively small fluctuations in plasma concentrations between dosing intervals at steady state. Therefore, although amlodipine's structure is similar to other dihydropyridine derivatives, its pharmacokinetic characteristics are significantly different, making it suitable for single-dose daily administration. A randomized, two-way crossover study enrolled 18 healthy male volunteers, comparing the pharmacokinetics and pharmacodynamics of two dosage forms (amlodipine nicotinate (experimental group) and amlodipine besylate (control group)). Subjects received a single 5 mg dose of amlodipine, with a 4-week washout period between doses. Blood samples were collected within 144 hours after administration for pharmacokinetic analysis of amlodipine. Systolic blood pressure, diastolic blood pressure, and pulse rate were recorded immediately before each blood draw. All subjects completed both treatment phases, and no serious adverse events occurred during the study. Following a single dose, the mean AUC_0-∞ and C_max values of the test formulation were 190.91±60.49 ng·hr/mL and 3.87±1.04 ng/mL, respectively, while those of the reference formulation were 203.15±52.05 ng·hr/mL and 4.01±0.60 ng/mL, respectively. The 90% confidence intervals for the mean ratios of AUC_0-∞ and C_max of the test and reference formulations were all within the pre-specified 80%–125% equivalence range. Pharmacodynamic characteristics, including systolic blood pressure, diastolic blood pressure, and pulse rate, showed no significant differences between the two formulations. The two amlodipine formulations exhibit similar pharmacokinetic and pharmacodynamic characteristics. The new formulation, amlodipine nicotinate, is pharmacokinetically comparable to the currently marketed amlodipine besylate, with similar absorption rates and extent.

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Metabolism/Metabolites
Amlodipine is primarily (approximately 90%) metabolized in the liver to inactive metabolites, with 10% of the parent compound and 60% of the metabolites excreted in the urine. In vitro studies have shown that approximately 93% of circulating amlodipine in hypertensive patients is bound to plasma proteins. Amlodipine's unique pharmacological properties include near-complete absorption, a late peak plasma concentration, high bioavailability, and slow hepatic metabolism. Amlodipine is primarily (approximately 90%) metabolized in the liver to inactive metabolites, with 10% of the parent compound and 60% of the metabolites excreted in the urine. The metabolism of the dihydropyridine calcium channel blocker (R,S)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-1-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine (amlodipine) has been studied in animals and humans using 14C-labeled drugs. Its metabolic profile is complex; 18 metabolites have been isolated from the urine of rats, dogs, and humans. Based on chromatographic and mass spectrometric evidence, we proposed the structures of the major metabolites and validated them by synthesizing well-defined reference compounds. We used gas chromatography-mass spectrometry (GC-MS) and pressure liquid chromatography-online thermal spray mass spectrometry (HPLC-OLSPMS) to directly analyze the underrivatized compounds in urine, comparing all reference compounds with the isolated metabolites. The metabolites are primarily pyridine derivatives. This paper describes the structural identification methods and the proposed metabolic pathways, demonstrating that the metabolic pattern of amlodipine in humans shares common characteristics with that in rats and dogs. This study aimed to determine the metabolic profile of amlodipine (racemic mixture and S-isomer) in human liver microsomes (HLM) and to identify cytochrome P450 (P450) enzymes involved in M9 formation. Liquid chromatography/mass spectrometry analysis showed that amlodipine was primarily converted to M9 during HLM incubation. M9 further underwent O-demethylation, O-dealkylation, and oxidative deamination reactions, generating various pyridine derivatives. This observation is consistent with the metabolism of amlodipine in humans. Incubation of amlodipine with human liver microsomes (HLM) in the presence of selective P450 inhibitors showed that both ketoconazole (a CYP3A4/5 inhibitor) and CYP3cide (a CYP3A4 inhibitor) completely blocked M9 formation, while other chemical inhibitors of P450 enzymes had little effect. Furthermore, the metabolism of amlodipine in expressed human P450 enzymes showed that only CYP3A4 exhibited significant activity in the dehydrogenation of amlodipine. The metabolite profiles of the racemic mixture and S-isomer of amlodipine were very similar to the P450 reaction phenotypic data. These results indicate that CYP3A4, rather than CYP3A5, plays a crucial role in the metabolic clearance of amlodipine in humans. This study employed liquid chromatography-mass spectrometry (LC/MS) to investigate the metabolomic profile of amlodipine, a commonly used calcium channel blocker. We used two different mass spectrometers—a triple quadrupole (QqQ) mass spectrometer and a quadrupole time-of-flight (Q-TOF) mass spectrometer—to obtain structural information on amlodipine metabolites. The metabolites were generated by incubating amlodipine with rat primary hepatocyte cultures. Analysis of the rat hepatocyte incubation medium using LC-MS/MS detected 21 phase I and phase II metabolites. We acquired and resolved the product ion spectra of these metabolites and proposed their structures. Precise mass measurements were performed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF) to determine the elemental composition of the metabolites, thus validating their hypothesized structures. Phase I metabolic changes were primarily observed, including dehydrogenation of the dihydropyridine core and side-chain reactions such as ester hydrolysis, hydroxylation, N-acetylation, oxidative deamination, and combinations thereof. The only phase II metabolite detected was the glucuronide of the amlodipine dehydrogenated and deaminated metabolite. Based on our analysis of the detected and identified metabolites, several in vitro metabolic pathways of amlodipine in rats were proposed.
Biological half-life
The terminal elimination half-life is approximately 30–50 hours.
The plasma elimination half-life in patients with impaired liver function is 56 hours; slow titration should be performed when administering to patients with severe hepatic impairment.
Plasma elimination is biphasic, with a terminal elimination half-life of approximately 30–50 hours.
……After oral administration, the terminal elimination half-life of amlodipine is 40 to 50 hours. ……

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In humans ([1][2]): Oral bioavailability of amlodipine = 70-80% (5 mg dose); plasma half-life (t₁/₂) = 35-50 hours; maximum plasma concentration (Cmax) = 8-12 ng/mL 6-12 hours after oral administration [2]
-Distribution ([1][2]): Volume of distribution (Vd) = 21 L/kg (human); widely distributed in vascular tissue (tissue/plasma concentration ratio = 10:1) [2]
-Metabolism ([1][2]): Metabolized in the liver by CYP3A4 (inactive metabolites); 90% of the dose is excreted in urine/feces as metabolites (10% is excreted unchanged) [1]

Toxicity Summary
Identification and Uses: Amlodipine is a calcium channel blocker used as an antihypertensive and vasodilator. Human Exposure and Toxicity: One patient ingested 250 mg of amlodipine without symptoms. Another patient ingested 120 mg, underwent gastric lavage, and maintained normal blood pressure. A third patient ingested 105 mg and experienced hypotension (90/50 mmHg), which was restored to normal after plasma resuscitation. A 19-month-old infant ingested 30 mg (2 mg/kg) without hypotension, but had a heart rate of 180 bpm. Children ingesting >10 mg are 4.4 times more likely to experience a clinically significant reaction than children ingesting ≤5 mg. Hypotension can occur in children even with doses as low as 2.5 mg of amlodipine. Animal Studies: Rats and mice fed amlodipine maleate for two years at daily doses of 0.5, 1.25, and 2.5 mg/kg showed no carcinogenic effects. Amlodipine has been shown to prolong labor in rats. During major organogenesis, no teratogenicity or other embryo/fetal toxicity was observed in rats or rabbits receiving doses up to 10 mg/kg. However, intrauterine mortality increased approximately fivefold, and litter size decreased by 50%. Mutagenicity studies of amlodipine maleate showed no effects at the gene or chromosomal level.

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Hepatotoxicity
Long-term amlodipine treatment was associated with a lower incidence of serum enzyme elevations, similar to those in matched controls. Enzyme elevations are usually mild, transient, and asymptomatic, and may resolve spontaneously even during continued treatment. Clinically significant liver injury caused by amlodipine is rare, reported only in isolated cases. In the few reported specific cases, the latency period for liver injury is typically 4 to 12 weeks, but prolonged latency periods (10 months and several years) have also been reported. The latency period for recurrence of liver injury after re-exposure to amlodipine is short, including some cases of recurrence following liver injury caused by other calcium channel blockers. The pattern of serum enzyme elevation is usually mixed or cholestatic. No rash, fever, or eosinophilia has been reported, and autoantibodies are atypical. Probability score: C (Probably but rarely causes clinically significant liver injury). Effects during pregnancy and lactation: ◉ Overview of use during lactation: Limited information suggests that amlodipine concentrations in breast milk are typically low, and plasma concentrations in breastfed infants are undetectable. Maternal use of amlodipine during lactation has not caused any adverse effects on breastfed infants. If a mother needs to take amlodipine, this is not a reason to discontinue breastfeeding. ◉ Effects on breastfed infants: A woman started taking amlodipine 5 mg daily 2 weeks postpartum to treat hypertension. Her exclusively breastfed infant received regular checkups and was in good health with normal physical and neurological development at 3 months of age. A woman was given amlodipine 2.5 mg twice daily during pregnancy due to hypertension caused by glomerulonephritis. On day 2 postpartum, the dose was increased to 5 mg twice daily. Her exclusively breastfed infant had normal growth and development in the first year of life, with no adverse reactions observed. A preterm infant born at 32 weeks of gestation was exclusively breastfed from day 7 to day 20 postpartum. The infant's mother was taking amlodipine and labetalol for hypertension, but the dosage was not specified. The infant experienced episodes of apnea unrelated to amlodipine. At 2 months of age, growth and development were slightly below normal. 31 postpartum women with gestational hypertension were given amlodipine 5 mg once daily, with dose increases as needed to maintain blood pressure at 140/90 mmHg or below. Their breastfed infants (feeding extent not specified) did not experience adverse cardiovascular reactions within 3 weeks postpartum, but the specific measurement methods were not specified.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
Approximately 98%.

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Interactions
This open-label, crossover study aimed to determine, based on pharmacokinetics and safety, whether there was evidence of an interaction between the angiotensin II receptor antagonist telmisartan and the class II (dihydropyridine) calcium channel antagonist amlodipine. In a two-way crossover trial, 12 healthy white men were randomized to receive amlodipine 10 mg once daily for 9 days, concurrently or separately from telmisartan 120 mg. After a washout period of ≥13 days, subjects were switched to another drug regimen. When amlodipine was administered alone, the geometric mean of the main pharmacokinetic parameters at steady state (day 9) was as follows: peak plasma concentration (Cmax) 17.7 ng/mL, area under the plasma concentration-time curve (AUC) 331 ng·hr/mL, and renal clearance 39.5 mL/min, with 8% of the total amlodipine dose excreted renally. When telmisartan was administered concurrently, the above parameters were 18.7 ng/mL, 352 ng·hr/mL, and 43.0 mL/min, respectively, with 9.4% of the total amlodipine dose excreted renally. The 90% confidence intervals (CIs) for these steady-state parameter ratios were 0.97 to 1.14 for Cmax and 0.98 to 1.16 for AUC; both were within the pre-specified bioequivalence reference range (0.8 to 1.25). Due to significant differences in urinary amlodipine excretion among subjects, the bioequivalence of renal clearance could not be confirmed. Whether used alone or in combination with telmisartan, adverse reactions were few, mild to moderate, and transient. Except for blood pressure, vital signs and clinical laboratory indicators were not affected by either drug. These results indicate that combination therapy with telmisartan and amlodipine is feasible because the main pharmacokinetic parameters of amlodipine did not change clinically significant in the presence of telmisartan, and the safety profile of the combination therapy was comparable to that of amlodipine alone. Amlodipine is a typical calcium channel blocker commonly used to treat hypertension. This study investigated potential drug interactions between amlodipine and the co-administered antibiotic (ampicillin) in rats; and analyzed changes in gut microbiota metabolic activity and the pharmacokinetic pattern of amlodipine after ampicillin treatment. In fecal enzyme-incubated samples from humans and rats, amlodipine was metabolized to produce a major pyridine metabolite. With prolonged incubation, the remaining amlodipine decreased, while the production of the pyridine metabolite increased, indicating that gut microbiota is involved in the metabolism of amlodipine. Pharmacokinetic analysis showed that, compared with the control group, the systemic exposure of amlodipine in rats treated with antibiotics was significantly increased. These results indicate that antibiotic intake may increase the bioavailability of amlodipine by inhibiting the metabolic activity of intestinal microorganisms, thereby altering its therapeutic efficacy. Therefore, caution and clinical monitoring are required when using amlodipine in combination with antibiotics.
1. This study used the acetic acid writhing test and tail-flick test to detect the analgesic effect of subcutaneous (SC), intraventricular (ICV), and intrathecal (IT) administration of amlodipine in mice. The combined effects of amlodipine with morphine and ketorolac were also tested. The functional interactions between amlodipine and morphine or ketorolac were determined using isoline analysis. 2. Subcutaneous injection (0.1, 1.25, 2.5, 5, and 10 mg/kg), intraventricular injection (2.5, 5, 10, and 20 μg/mouse), and intravenous injection (2.5, 5, 10, and 20 μg/mouse) of amlodipine showed dose-dependent analgesia in the writhing test, but had no effect on tail-flip latency. Isoline analysis showed an additive effect of amlodipine with morphine or ketorolac in the writhing test. 3. These results suggest that amlodipine may induce analgesia by reducing intracellular calcium ion concentration and enhance the analgesic effects of morphine and ketorolac. …This study aimed to investigate the drug interaction between amlodipine and simvastatin. A total of 8 patients with hypercholesterolemia and hypertension were included. Subjects received oral simvastatin (5 mg/day) for 4 weeks, followed by oral amlodipine (5 mg/day) in combination with simvastatin (5 mg/day) for 4 weeks. Combination therapy with simvastatin increased the peak concentration (Cmax) of the HMG-CoA reductase inhibitor from 9.6 ± 3.7 ng/mL to 13.7 ± 4.7 ng/mL (p < 0.05) and the area under the concentration-time curve (AUC) from 34.3 ± 16.5 ng·h/mL to 43.9 ± 16.6 ng·h/mL (p < 0.05), but did not affect the cholesterol-lowering effect of simvastatin. ...
For more complete interaction data (13 items in total) for amlodipine (AMLODIPINE), please visit the HSDB record page.

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Common adverse reactions ([1][2]): peripheral edema (10-20% of patients, dose-dependent), headache (5-10%), flushing (3-7%); can be relieved by adjusting the dose [2]
-Liver safety ([1][2]): mild, transient increase in serum ALT/AST (≤2 times the normal value) in 2-3% of patients [1]
-Plasma protein binding rate ([1][2]): binding rate to human plasma proteins is 93-98% (ultrafiltration method) [2]
-In the 28-day A431 study ([3]): no significant weight loss (>8%); serum BUN (18 ± 3 mg/dL) and creatinine (0.8 ± 0.1 mg/dL) were within the normal range [3]

[1]. Amlodipine.

[2]. Amlodipine. A reappraisal of its pharmacological properties and therapeutic use in cardiovascular disease [published correction appears in Drugs 1995 Nov;50(5):896]. Drugs. 1995;50(3):560-586.

[3]. Antitumor effects of amlodipine, a Ca2+ channel blocker, on human epidermoid carcinoma A431 cells in vitro and in vivo. Eur J Pharmacol. 2004 May 25;492(2-3):103-12.

[4]. The effects of anti-hypertensive drugs and the mechanism of hypertension in vascular smooth muscle cell-specific ATP2B1 knockout mice. Hypertens Res. 2018 Feb;41(2):80-87.

Therapeutic Uses

Antihypertensive; Calcium Channel Blocker; Vasodilator
Novask is indicated for the treatment of hypertension to lower blood pressure. …Novask can be used alone or in combination with other antihypertensive drugs. /US Product Label/
Novask is indicated for the treatment of symptoms of chronic stable angina. Novasy can be used alone or in combination with other antianginal drugs. /US Product Label/
Novask is indicated for the treatment of confirmed or suspected vasospastic angina. Novasy can be used alone or in combination with other antianginal drugs. /Included in US Product Label/
For more complete data on the therapeutic uses of amlodipine (6 types), please visit the HSDB record page.

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Drug Warnings
Amlodipine clearance is reduced in elderly patients, with an AUC increase of approximately 40-60%. Therefore, the dosage of amlodipine should be carefully selected, and treatment is usually started at the lower end of the recommended dose range. Elderly patients should also be considered for their higher incidence of hepatic, renal, and/or cardiac impairment, as well as concomitant diseases and drug treatments. Amlodipine clearance is reduced in patients with impaired liver function, with an AUC increase of approximately 40-60%. A lower initial dose is recommended, followed by slow titration of subsequent doses. When amlodipine is used in combination with other drugs (e.g., other antihypertensive drugs, atorvastatin) in fixed-dose formulations, in addition to the precautions for amlodipine itself, precautions for concomitant use, contraindications, and interactions should be considered. Furthermore, precautions for each drug in the combination formulation in specific populations (e.g., pregnant or lactating women, patients with hepatic or renal impairment, elderly patients) should be considered. Although some calcium channel blockers have been shown to worsen clinical symptoms in patients with heart failure, no evidence of worsening heart failure (based on exercise tolerance, New York Heart Association (NYHA) functional classification, symptoms, or left ventricular ejection fraction) or adverse effects on overall survival and cardiac disease incidence has been observed in controlled studies of amlodipine in patients with heart failure. In these studies, patients treated with amlodipine and those treated with placebo had similar cardiac morbidity and all-cause mortality. In patients with moderate to severe heart failure, amlodipine clearance was reduced, with an increase in the area under the concentration-time curve (AUC) of approximately 40-60%. For more complete data on drug warnings for amlodipine (15 in total), please visit the HSDB record page.

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Pharmacodynamics
General Pharmacodynamic Actions: Amlodipine has a strong affinity for cell membranes and modulates calcium ion influx by inhibiting specific membrane calcium channels. Its unique binding properties contribute to its long-lasting effect and allow for reduced dosing frequency. Hemodynamic Actions: In patients diagnosed with hypertension, administration of therapeutic doses of amlodipine causes vasodilation, thereby reducing blood pressure in both supine and standing positions. During these blood pressure reductions, prolonged use of amlodipine does not cause clinically significant changes in heart rate or plasma catecholamine levels. Acute intravenous amlodipine can lower arterial blood pressure and increase heart rate in patients with chronic stable angina. However, clinical studies have shown that long-term oral amlodipine has not caused clinically significant changes in heart rate or blood pressure in patients diagnosed with angina and with normal blood pressure. Long-term once-daily oral administration maintains its antihypertensive effect for at least 24 hours. Electrophysiological effects: Amlodipine does not alter sinoatrial node function or atrioventricular conduction in animals or humans. In patients diagnosed with chronic stable angina, intravenous administration of 10 mg amlodipine did not cause clinically significant changes in AH and HV conduction or sinoatrial node recovery time after cardiac pacing. Similar results were obtained in patients taking amlodipine and beta-blockers concurrently. In clinical trials of amlodipine combined with beta-blockers in patients diagnosed with hypertension or angina, no adverse effects on ECG parameters were observed. In clinical studies involving only patients with angina, amlodipine did not alter ECG intervals or cause high-degree atrioventricular block. Effects of amlodipine on angina: Amlodipine can relieve chest pain symptoms associated with angina. In patients diagnosed with angina, a single daily dose of amlodipine can increase total exercise time, angina attack duration, and the time to 1 mm ST segment depression on electrocardiogram, reduce the frequency of angina attacks, and decrease the need for nitroglycerin tablets.

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Amlodipine (UK-48340; Norvasc) is a long-acting dihydropyridine (DHP) L-type calcium channel blocker (CCB) approved for the treatment of hypertension, chronic stable angina, and vasospastic angina[1][2]
- Its antihypertensive mechanism: by inhibiting Ca²⁺ influx into vascular smooth muscle cells (VSMCs) via CaV1.2, thereby reducing VSMC contraction and peripheral vascular resistance; no negative inotropic/negative chronotropic effects at therapeutic doses[1][4]
- Preclinical antitumor activity in A431 cells is attributed to disruption of Ca²⁺ signaling, inhibiting cell proliferation and inducing apoptosis (not yet approved for indication)[3]
- In ATP2B1-KO mice (a hypertension model with impaired Ca²⁺ efflux), it normalized [Ca²⁺]i in vascular smooth muscle cells, confirming that Ca²⁺ homeostasis is a key therapeutic target[4]

C20H25CLN2O5

408.88

408.145

C, 58.75; H, 6.16; Cl, 8.67; N, 6.85; O, 19.57

88150-42-9

Amlodipine maleate;88150-47-4;Amlodipine besylate;111470-99-6;Amlodipine mesylate;246852-12-0;Amlodipine-1,1,2,2-d4 maleate;1185246-15-4;Amlodipine-d4;1185246-14-3

2162

White to off-white solid powder

1.2±0.1 g/cm3

527.2±50.0 °C at 760 mmHg

178-179ºC

272.6±30.1 °C

0.0±1.4 mmHg at 25°C

1.546

4.16

2

7

10

28

647

0

O=C(C1C(C2C(Cl)=CC=CC=2)C(C(OCC)=O)=C(COCCN)NC=1C)OC

HTIQEAQVCYTUBX-UHFFFAOYSA-N

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

3-O-ethyl 5-O-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 3 mg/mL (7.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 3 mg/mL (7.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3 mg/mL (7.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)