Long-acting dihydropyridine calcium antagonists. 1. 2-Alkoxymethyl derivatives incorporating basic substituents

Arrowsmith, John; Campbell, Simon F.; Cross, P. E.; Stubbs, J. K.; Burges, Roger A.; Gardiner, Donald G.; Blackburn, K J

doi:10.1021/jm00159a022

Cited by 205 publications

(104 citation statements)

References 0 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…Amlodipine, a 1,4-dihydropyridine derivative of nifedipine, has a highly stereospecific property on the calcium channels. The affinity of its levorotary (-)-enantiomer to the calcium channels is 1,000 times superior to that of its dextrorotary (+)-enantiomer (1). On the basis of this stereospecificity, the chloroquine potentiating actions of the racemic mixture and the (+)-enantiomer of amlodipine were compared in this study.…”

mentioning

confidence: 99%

In vitro and in vivo potentiation of chloroquine against malaria parasites by an enantiomer of amlodipine

Deloron

Basco

Dubois

et al. 1991

Antimicrob Agents Chemother

View full text Add to dashboard Cite

A combination of chloroquine and amlodipine, a derivative of 1,4-dihydropyridine calcium channel blocker, was tested against Plasmodium falciparum in vitro and P. yoelii in mice. The dextrorotary enantiomer of amlodipine, practically devoid of calcium channel blocking action, increased chloroquine accumulation inside the infected mouse erythrocytes and potentiated chloroquine action against the resistant strains of P. falciparum in vitro and P. yoelii in mice. Unlike the racemate, the dextrorotary amlodipine was not toxic to the host animal, even at the highest dose of 250 mg/kg. No potentiating effect was noted in the chloroquine-susceptible strains of P. falciparum. The results of this study indicate that chloroquine potentiation of amlodipine is probably independent of calcium channels and that a combination therapy of the dextrorotary enantiomer of amlodipine and chloroquine might be a potentially useful therapeutic strategy against chloroquine-resistant falciparum malaria.Chloroquine has been the drug of choice for treating Plasmodium falciparum malaria for more than 40 years. However, the prophylactic and therapeutic utility of chloroquine is largely limited today because of the spread of the chloroquine-resistant strains of P. falciparum in most malaria-endemic regions (5). Therefore, new therapeutic approaches are urgently needed.The mechanism of chloroquine resistance is thought to involve an enhanced drug efflux from the drug-resistant malaria parasites (17). This efflux process is supposed to be responsible for the failure of chloroquine to accumulate inside erythrocytes parasitized by resistant parasites to the extent that has been observed with susceptible parasites (7,21,32). This efflux process can be inhibited by several calcium channel blockers (22,29). Similar observations were reported with tricyclic antidepressants (4) and tricyclic antihistaminics (25). The latter agents possess an indirect calcium antagonist action on either calmodulin, a calciumbinding protein (27), or other calcium-dependent enzymes (20).The use of combination therapy with chloroquine and calcium antagonists is probably unsuitable in cases of human malaria because of the high doses of calcium antagonists necessary to reverse chloroquine resistance (4). One of the possible means to circumvent this problem of host toxicity may be the use of stereospecific drugs (2, 16), since the dextrorotatory (+)-enantiomer of verapamil has been shown to reverse chloroquine resistance in vitro (37). Amlodipine, a 1,4-dihydropyridine derivative of nifedipine, has a highly stereospecific property on the calcium channels. The affinity of its levorotary (-)-enantiomer to the calcium channels is 1,000 times superior to that of its dextrorotary (+)-enantiomer (1). On the basis of this stereospecificity, the chloroquine potentiating actions of the racemic mixture and the (+)-enantiomer of amlodipine were compared in this study. We report that (+)-amlodipine potentiated chloroquine in vitro and in vivo, without lethal effects, and led to a * Corr...

show abstract

mentioning

confidence: 99%

In vitro and in vivo potentiation of chloroquine against malaria parasites by an enantiomer of amlodipine

Deloron

Basco

Dubois

et al. 1991

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Amlodipine besylate [ Figure 1B], chemically designated as 2-[(2-aminoethoxy)-methyl]-4-(2-chlorophenyl) 1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid-3 ethyl-5 methyl ester, is a calcium channel blocker used to treat hypertension and angina (Arrowsmith et al, 1986;O` Neil et al, 2006). The drug is found to metabolize in the liver and the produced metabolites are excreted via urine along with some unchanged drug (Abernethy, 1989;Meredith, Elliott, 1992).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous estimation of rosuvastatin and amlodipine in pharmaceutical formulations using stability indicating HPLC method

Ashfaq

Akhtar

Mustafa

et al. 2014

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

A viable cost-effective and isocratic approach employing C-18 column (250 mm × 4.6 mm, 5 µm) based HPLC has been utilized to separate and estimate the drugs, rosuvastatin, amlodipine and their stress induced degradation products, simultaneously in pharmaceutical formulations. Focused on ICH guideline parameters, the efficient separation of both drugs and their degradation products was achieved by optimizing a 30:70 (v/v) solvent mixture of acetonitrile and 0.1 M ammonium acetate buffer (pH 5) as mobile phase. The flow rate of the mobile phase was 1.5 mL/min and all the detections were carried out at 240 nm using UV detector. The method was linear in the concentration range of 1-200 µg/mL for rosuvastatin with 0.996 coefficient of determination value. For amlodipine, linearity was in the range of 0.5-100 µg/ml with 0.994 coefficient of determination value. Both the drugs along with their degradation products were separated in less than twenty minutes. The results of within-day and between-day precision were varied from 0.72 to 1.81% for rosuvastatin and 0.83 to 1.88% for amlodipine. The results show that this ICH validated method can be employed successfully for the routine as well as stability quantification of both the active ingredients simultaneously in pharmaceutical formulations. Utilizou-se abordagem de viabilidade custo-efetividade e isocrática, baseada em CLAE, empregando coluna C-18 (250 mm x 4,6 mm, 5 µm) para separar e avaliar os fármacos, rosuvastatina, anlodipino e seus produtos de degradação induzida por estresse, simultaneamente, em formulações farmacêuticas. Focada nos parâmetros das diretrizes da ICH, a separação eficiente de ambos os fármacos e de seus produtos de degradação foi obtida por meio da otimização da fase móvel com mistura de solventes 30:70 (v/v), respectivamente, acetonitrila e tampão acetato de amônio O,1 M (pH 5). A velocidade de fluxo da fase móvel foi de 1,5 mL/min e todas as detecções foram realizadas em 240 nm, utilizando detector de UV. O método foi linear no intervalo de concentração de 1-200 µg/mL para a rosuvastatina com coeficiente de determinação 0,996. Para o anlodipino, a linearidade ficou na faixa de 0.5-100 µg/mL, com coeficiente de determinação 0,994. Ambos os fármacos, junto com seus produtos de degradação, foram separados em menos de vinte minutos. Os resultados de precisão intra-dia e inter-dia variaram de 0,72 a 1,81% para a rosuvastatina e de 0,83 a 1,88%, para o anlodipino. Os resultados mostram que este método validado pelo ICH pode ser empregado com sucesso tanto para a rotina quanto para a quantificação simultânea da estabilidade de ambos os ingredientes ativos em formulações farmacêuticas.Unitermos: Cromatografia Líquida de Alto Desempenho/análise quantitative. Rosuvastatina/determinação quantitativa. Anlodipino/determinação quantitativa. Formulações farmacêuticas/análise quantitativa.

show abstract

“…1,4-DHP's attracted more attention, thanks to its presence in the coenzyme, diphospho pyridine nucleotide (DPNH) [2] and identification as bio-active material. In the present scenario many representatives have been commercialised such as nifedipine [3], felodipine [4], nicardipine [5], amlodipine [6] and even more have made their presence felt in the market [7] in the treatment of angina and hypertension. The activity profiles of 1,4-DHP's were further expanded as they were detected to possess anti-tumor [8], antiinflammatory [9], anticonvulsant activity [10], antitubercular activity [11,12] cerebral antischemic activity in the treatment of Alzheimer's disease, PAF-acether antagonists [13].…”

Section: Introductionmentioning

confidence: 99%

One-pot, multicomponent synthesis of symmetrical Hantzsch 1,4-dihydropyridine derivatives using glycerol as clean and green solvent

Sohal

Goyal

Sharma³

et al. 2014

Eur. J. Chem.

View full text Add to dashboard Cite

Long-acting dihydropyridine calcium antagonists. 1. 2-Alkoxymethyl derivatives incorporating basic substituents

Cited by 205 publications

References 0 publications

In vitro and in vivo potentiation of chloroquine against malaria parasites by an enantiomer of amlodipine

In vitro and in vivo potentiation of chloroquine against malaria parasites by an enantiomer of amlodipine

Simultaneous estimation of rosuvastatin and amlodipine in pharmaceutical formulations using stability indicating HPLC method

One-pot, multicomponent synthesis of symmetrical Hantzsch 1,4-dihydropyridine derivatives using glycerol as clean and green solvent

Contact Info

Product

Resources

About