Dihydropyridine calcium antagonists

H. Fujimoto, I. Nishino, K. Ueno and T. Umeda, Determination of the enantiomers of a new 1,4-dihydropyridine calcium antagonist in dog plasma achiral / chiral coupled high performance liquid cliromatography with electrochemical detection , 7. Pharm. Sci. 82 319-322(1993). 

Dihydropyridine calcium antagonist RP Ion exchange (Nucleosil SA) Ovamucoid Fujitomo et al., 1993... 

M. Yabuki, F. Shono, I. Nakatsuka, A. Yoshitake, Novel Cleavage of the 1,2,4-Oxadia-zole Ring in Rat Metabobsm of SM-6586, a Dihydropyridine Calcium Antagonist , Drug Metab. Dispos. 1993, 21, 1167 - 1169. 

Sevanian, A., Shen, L., and Ursini, P., 2000, Inhibition of LDL oxidation and oxidized LDL-induced cytotoxicity by dihydropyridine calcium antagonists, Pbami. Res. 17 999-1006. 

Dihydropyridine calcium Antagonists Myocardial infarction /S-blockers (non-ISA)... 

Rossetti ZL, Pani L, Kuzmin A, et al Dihydropyridine calcium antagonists prevent cocaine-, but not amphetamine-, induced dopamine release and motor activity in rats. Acta Physiol Hung 75 (suppl) 249-250, 1990 Rossetti ZL, Lai M, Hmaidan Y, et al Depletion of mesohmbic dopamine during behavioural despair partial reversal by chronic imipramine. Eur J Pharmacol 242 313-315, 1993... 

The EOs reduced the contraction induced by acetylcholine, histamine [226-228, 210, 225, 232, 233], carbachol (muscarinic receptor activator) [237] and 5-hydroxytryptamine [229]. The EOs were found to relax intestinal smooth muscle by reducing the influx of Ca [227, 234], K+ [210, 224-226, 229, 230] and Ba [229, 237]. However, other reports have shown that lavender and geranium EOs were unlikely to act as cationic channel blockers [232]. The activities of the EOs resembled those of dicyclomine and atropine (muscarinic receptor antagonists) and dihydropyridine (calcium antagonist) by producing smooth-muscle relaxation [225, 236]. 

Katoh M, Nakajima M, Shimada N, et al. Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol 2000 55 843-852. 

Zhang et al. described a HPLC method for the simultaneous determination of six different dihydropyridine calcium antagonists (including nimodipine) in plasma [30]. After extraction with ethyl ether/ -heptane (1 1) and centrifugation, the organic phase was heated at 50°C and the residue dissolved in aqueous 60% acetonitrile (the mobile phase). An Ultrasphere 5 pm ODS column (25 cm x 4.6 mm i.d.) was used as the means of separation. The mobile phase flow rate was 1 mL/min, and detection was effected at 238 nm. The calibration graphs were linear over the range of 50 ng/mL-6.4 pg/mL, with a detection limit of 5 ng/mL. 

Gilar et al. have also applied CE to the separation of dihydropyridine calcium antagonists [25]. Their method used an uncoated capillary (76 cm x 75 pm i.d.) at 20 kV, a running buffer of 20-25 M phosphate-borate buffer (pH 9-9.5) containing 1% urea, and detection at 240 nm. The buffer also contained 10 mM p-cyclodextrin, and varying amounts of SDS. 

The main objective of the project was to identify a new potent and selective dihydropyridine calcium antagonist which was endowed with a sustained duration of action and was amenable to become a once-daily antihypertensive drug. 

However, as already mentioned earlier, high pressure liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) has evolved in the last few years as the major bioanalytical technique for the bioanalysis of analytes in biological matrices. This is reflected also in a number of LC-MS/MS assays for the determination of dihydropyridine calcium antagonists in biological fluids (Carvalho et al. 2001, Schug et al. 2002 Kang et al. 2004). 

Alker D, Campbell SF, Cross PE et al (1990) Long-acting dihydropyridine calcium antagonists. 4. Synthesis and structure-activity relationships for a series of basic and non basic derivatives of 2[(2-aminoethoxy)methyl]-l, 4-dihydropyridine calcium antagonists. J Med Chem 33 585-591... 

Oxcarbazepine can decrease plasma levels of hormonal contraceptives and dihydropyridine calcium antagonists... 

Abernethy DR, Gutkowska J, Winterbottom LM. Effects of amlodipine, a long-acting dihydropyridine calcium antagonist in aging hypertension Pharmacodynamics in relation to disposition. Clin Pharmacol Ther 1990 48 7 86. 

Dihydropyridine calcium antagonists Dansyl amino acids... 

A randomized comparison of oral atenolol and bisoprolol in 334 patients with acute myocardial infarction was associated with drug withdrawal in 70 patients (21%) because of significant bradydysrhythmias, hypotension, heart failure, and abnormal atrioventricular conduction (40). Logistic regression analysis suggested that critical events were more likely to occur in patients who were pretreated with dihydropyridine calcium antagonists. 

Abrupt switch of therapy from mibefradil to other dihydropyridine calcium antagonist was reported to cause shock, fatal in one case, in four patients also taking beta-blockers (8). 

Dhein S, Salameh A, Berkels R, Klaus W. 1999. Dual mode of action of dihydropyridine calcium antagonists a role for nitric oxide. Drugs 58 397 104... 

Kubota K, Pearce GL, Inman WH. Vasodilation-related adverse events in diltia-zem and dihydropyridine calcium antagonists studied by prescription-event monitoring. Ear J Clin Pharmacol 1995 48 1-7. 

Mager PP, Coburn RA, Solo AJ, Triggle DJ, Rothe H. QSAR, diagnostic statistics and molecular modelling of 1,4-dihydropyridine calcium antagonists A difficult road ahead. Drug Des Discov 1992 8 273-89. 

Gilar, M., Uhrova, M.,Tesarova, E. Enantiomer separation of dihydropyridine calcium antagonists with cyclodextrins as chiral selectors structural correlation, J. Chromatogr. B., 1996, 681, 133-141. 

A new route to pyridazine analogues of dihydropyridine calcium antagonists has been devised. Ethyl l,3-dithiolane-2-carboxylate was found to add efficiently, as its lithium salt, to benzylidene derivatives prepared from aryl aldehydes and diethylmalonate or ethyl acetoacetate the dithiolane adducts were readily deprotected using NBS (Scheme 98). The resultant diketo derivatives (121) were cyclized with hydrazine to give either 1,4-dihydropyridazines (122) or l,4,5,6-tetrahydro-6-... 

Niwa, T. Tokuma, Y. Nakagawa, K. Noguchi, H. Stereoselective oxidation of nilvadipine, a new dihydropyridine calcium antagonist, in rat and dog liver. Drug Metab. Dispos. 1989, 17, 64-68. 

Madsen JK, Jensen JD, Jensen LW, Pederaen EB. Pharmacokinetic interacticn between cy-clo rine and the dihydropyridine calcium antagonist felodipine. Eur J Clin Pharmacol (1996) 50,203-8. 

Y. lida, Y. Kinouchi, Y. Takeichi, T. Imai and M. Otagiri, Simultaneous determination of a new dihydropyridine calcium antagonist (MPC-1304) and its metabolite in dog plasma by high-performance liquid chromatography with electrochemical detection, J. Chromatogr., 1991, 571, 277-282. 

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