Calcium Antagonists

Kazda, S; Knorr, Andreas

doi:10.1007/978-3-642-74209-5_9

Cited by 17 publications

(7 citation statements)

References 284 publications

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“…They reported that the vasodilator hydralazine is equipotent in both strains at variance with nitrendipine less active on blood pressure in WKY than in SHR. Consistent with hemodynamic observations (Kazda and Knorr, 1990 ), these studies show that the activity profile of CCBs in cardiovascular system is different from the activity profile of classical arteriolar vasodilators. Furthermore, during chronic administration, the decrease of blood pressure occurs without change of the cardiac frequency (Frohlich, 1986 ).…”

Section: Acute Hemodynamic Effects Of Ccbssupporting

confidence: 90%

“…Calcium channel blockers do not cause sodium retention, an undesired effect that is observed with vasodilators including α-blockers, hydralazine, and minoxidil. By contrast, CCBs increase sodium excretion when administered acutely to hypertensive humans and animals (Kazda and Knorr, 1990 ). Mechanisms involved in the natriuresis evoked by CCBs are associated with various processes such as changes in renal hemodynamic, direct effects on renal tubules or indirect through regulation of vasoactive substances.…”

Section: Acute Hemodynamic Effects Of Ccbsmentioning

confidence: 99%

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Discovery and Development of Calcium Channel Blockers

2017

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In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan) and Heibrunn (USA) experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB) of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are important factors of their action. The high sensitivity of hypertensive animals is explained by the partial depolarization of their arteries. It is noted that they are arteriolar dilators and that they cannot be simply considered as vasodilators. The second part of this report provides key information about clinical usefulness of CCBs. A section is devoted to the controversy on their safety closed by the Allhat trial (2002). Sections are dedicated to their effect in cardiac ischemia, in cardiac arrhythmias, in atherosclerosis, in hypertension, and its complications. CCBs appear as the most commonly used for the treatment of cardiovascular diseases. As far as hypertension is concerned, globally the prevalence in adults aged 25 years and over was around 40% in 2008. Usefulness of CCBs is discussed on the basis of large clinical trials. At therapeutic dosage, they reduce the elevated blood pressure of hypertensive patients but don't change blood pressure of normotensive subjects, as was observed in animals. Those active on both L- and T-type channels are efficient in nephropat...

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Section: Acute Hemodynamic Effects Of Ccbssupporting

confidence: 90%

Section: Acute Hemodynamic Effects Of Ccbsmentioning

confidence: 99%

Discovery and Development of Calcium Channel Blockers

2017

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“…We used three antagonists which are highly specific in their action on individual types of calcium channels: the dihydropyridine compound nifedipine, inhibiting the L‐type (review Kazda & Knorr, 1990 ), and the peptides ω‐conotoxin GVIA and ω‐agatoxin IVA, inhibiting the N‐type and the P‐ and Q‐types of calcium channels, respectively (reviews Miljanich & Ramachandran, 1995 ; Tareilus & Breer, 1995 ; Uchitel, 1997 ). In addition, we used 100 n M ω‐conotoxin MVIIC, which is less selective in its inhibitory action on high‐voltage activated calcium channels ( Olivera et al ., 1994 ; McDonough et al ., 1996 ).…”

Section: Discussionmentioning

confidence: 99%

Calcium channels involved in the inhibition of acetylcholine release by presynaptic muscarinic receptors in rat striatum

Doležal

Tuček

1999

British J Pharmacology

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1 The mechanism of the inhibitory action of presynaptic muscarinic receptors on the release of acetylcholine from striatal cholinergic neurons is not known. We investigated how the electrically stimulated release of [ 3 H]-acetylcholine from superfused rat striatal slices and its inhibition by carbachol are aected by speci®c inhibitors of voltage-operated calcium channels of the L-type (nifedipine), N-type (o-conotoxin GVIA) and P/Q-type (o-agatoxin IVA). 2 The evoked release of [ 3 H]-acetylcholine was not diminished by nifedipine but was lowered by oconotoxin GVIA and by o-agatoxin IVA, indicating that both the N-and the P/Q-type (but not the L-type) channels are involved in the release. The N-type channels were responsible for approximately two thirds of the release. The release was 497% blocked when both o-toxins acted together.3 The inhibition of [ 3 H]-acetylcholine release by carbachol was not substantially aected by the blockade of the L-or P/Q-type channels. It was diminished but not eliminated by the blockade of the N-type channels. 4 In experiments on slices in which cholinesterases had been inhibited by paraoxon, inhibition of [ 3 H]-acetylcholine release by endogenous acetylcholine accumulating in the tissue could be demonstrated by the enhancement of the release after the addition of atropine. The inhibition was higher in slices with functional N-type than with functional P/Q-type channels. 5 We conclude that both the N-and the P/Q-type calcium channels contribute to the stimulationevoked release of acetylcholine in rat striatum, that the quantitative contribution of the N-type channels is higher, and that the inhibitory muscarinic receptors are more closely coupled with the Ntype than with the P/Q-type calcium channels.

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“…Whether similar interactions occur between other combinations of antihypertensive agents is not known. Calcium antagonists and fi-blockers have been shown to produce a synergistic effect on elevated blood pressure [6][7][8]. In addition, fi-adrenoceptor blockade has been found to reduce the vasodilatory side-effects of nifedipine [9] and less impairment of physical performance has been shown to occur with a calcium antagonist/fi-blocker combination than with a…”

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confidence: 98%

Effect of combined atenolol and nifedipine administration on psychomotor performance in normal subjects

Gerrard

Wheeldon

McDevitt

1995

Eur J Clin Pharmacol

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The aim of the present study was to evaluate the central effects of single doses of the beta-adrenoceptor antagonist atenolol and the calcium antagonist nifedipine retard, alone and in combination, in normal subjects. Twelve normal males received single oral doses of atenolol 100 mg, nifedipine retard 20 mg, atenolol 100 mg and nifedipine retard 20 mg in combination, diazepam 5 mg (active control), and each of two matching placebos in a double-blind, randomised fashion. Psychomotor performance was assessed using digit symbol substitution, letter cancellation (LCT), continuous attention, choice reaction time, finger tapping, immediate recall and short-term memory. Two flash fusion and critical flicker fusion thresholds were measured and subjective assessments made using visual analogue scales (VAS). Diazepam 5 mg significantly worsened LCT scores at 4h, significantly impaired alertness at 2 h and 4 h, and tended to increase reaction time and impair continuous attention and physiological measurements. Atenolol 100 mg alone significantly reduced alertness at 2 h and 4 h, and also tended to impair physiological measurements. Nifedipine retard 20 mg produced no significant psychomotor effects. Combined atenolol and nifedipine retard administration produced a small but significant improvement in continuous attention and a reduction in body sway, with no adverse effects being evident on performance or subjective awareness. The results suggest that no significant adverse effects on psychomotor performance are produced by single doses of atenolol 100 mg and nifedipine retard 20 mg when given together in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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Calcium Antagonists

Cited by 17 publications

References 284 publications

Discovery and Development of Calcium Channel Blockers

Discovery and Development of Calcium Channel Blockers

Calcium channels involved in the inhibition of acetylcholine release by presynaptic muscarinic receptors in rat striatum

Effect of combined atenolol and nifedipine administration on psychomotor performance in normal subjects

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