Clinical Studies on Veratrum Alkaloids

Meilman, Edward; Krayer, Otto

doi:10.1161/01.cir.1.2.204

Cited by 67 publications

(11 citation statements)

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“…and i.m.) for hypertension revealed a poor therapeutic window due to toxic side effects [34]. However, combination therapy reduced the dosage requirement whilst achieving its desired effect on VGSC [35].…”

Section: Resultsmentioning

confidence: 99%

Asteropsin A: An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2+ influx

Bowling

Fronczek

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Herein we report the discovery of a cystine-crosslinked peptide from Porifera along with high-quality spatial details accompanied by the description of its unique effect on neuronal calcium influx. Methods Asteropsin A (ASPA) was isolated from the marine sponge Asteropus sp., and its structure was independently determined using X-ray crystallography (0.87 Å) and solution NMR spectroscopy. Results An N-terminal pyroglutamate modification, uncommon cis proline conformations, and absence of basic residues helped distinguish ASPA from other cystine-crosslinked knot peptides. ASPA enhanced Ca2+ influx in murine cerebrocortical neuron cells following the addition of the Na+ channel activator veratridine but did not modify the oscillation frequency or amplitude of neuronal Ca2+ currents alone. Allosterism at neurotoxin site 2 was not observed, suggesting an alternative to the known Na+ channel interaction. Conclusions Together with a distinct biological activity, the origin of ASPA suggests a new subclass of cystine-rich knot peptides associated with Porifera. General significance The discovery of ASPA represents a distinctive addition to an emerging subclass of cystine-crosslinked knot peptides from Porifera.

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Section: Resultsmentioning

confidence: 99%

Asteropsin A: An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2+ influx

Bowling

Fronczek

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…The renewed interest in Veratrum alkaloids in the 1940s came at a lull in their medicinal use; Veratrum extracts had largely fallen out of favor by the early twentieth century due to difficulties with dosing, a result of the variable composition of the mixed alkaloid extracts (Meilman and Krayer 1950). One use for Veratrum extracts that persisted was in the treatment of eclampsia (Bryant and Flemming 1940).…”

Section: Modern Phytochemistry and Use Of Veratrum Alkaloids In The Tmentioning

confidence: 99%

“…Krayer et al demonstrated that protoveratrine could be used as a hypotensive agent, first in animal models and then in human trials, and in dosages that limited toxic effects (Krayer et al 1944; Meilman and Krayer 1950). Subsequent phytochemical analysis by numerous groups revealed that protoveratrine was actually a mixture of two tetraacyl esters of protoverine differing only at C-3 (Nash and Brooker 1953; Kupchan and Ayres 1960).…”

Section: Modern Phytochemistry and Use Of Veratrum Alkaloids In The Tmentioning

confidence: 99%

“…For one, the reflex action (Bezold–Jarisch reflex) responsible for the hypotensive effects of cevanine ester alkaloids was rapid in onset (minutes) but short lived in duration (<3 h). This made Veratrum alkloids only suitable for control of hypertensive emergencies and limited their use in chronic hypertension (Fries and Stanton 1948; Meilman and Krayer 1950; Meilman 1956; Winer 1960; Page and Sidd 1972). Also, the narrow range between toxic and therapeutic dosages (approximately 30 %) made titrating dosages in patients problematic, though the toxic effects could be rapidly reversed through the administration of atropine (Meilman 1956; Page and Sidd 1972).…”

Section: Modern Phytochemistry and Use Of Veratrum Alkaloids In The Tmentioning

confidence: 99%

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Medicinal history of North American Veratrum

Chandler

McDougal

2013

Phytochem Rev

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Plants belonging to the genus Veratrum have been used throughout history for their medicinal properties. During the nineteenth and twentieth centuries, phytochemical investigations revealed a host of steroidal alkaloids in Veratrum species, some of which are potent bioactives. This review discusses Veratrum species that grow in North America with a focus on the medicinal history of these plants and the steroidal alkaloids they contain. While significant reviews have been devoted to singularly describing the plant species within the genus Veratrum (botany), the staggering breadth of alkaloids isolated from these and related plants (phytochemistry), and the intricacies of how the various alkaloids act on their biological targets (physiology and biochemistry), this review will straddle the margins of the aforementioned disciplines in an attempt to provide a unified, coherent picture of the Veratrum plants of North America and the medicinal uses of their bioactive steroidal alkaloids.

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“…Meilman and Krayer (1950), in a study of the action of protoveratrine given intravenously in man, found that a significant fall of blood pressure could be produced without serious complications. In 1950, Freis et al reported the use of two previously undescribed crystalline alkaloids of veratrum viride, germitrine and germidine, both of which exhibited strong hypotensive activity in 439…”

mentioning

confidence: 99%

The Use of the Pure Veratrum Alkaloids Neogermitrine and Protoveratrine in Hypertension

Doyle¹,

Smirk²

1953

Heart

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The veratrum alkaloids were used clinically prior to the detailed knowledge of their pharmacology, Baker (1860) describing the successful treatment of a case of eclampsia. The pharmacological actions of the alkaloids were reported by Prevost in 1866, and von Bezold and Hirt (1867) attributed the fall in blood pressure and bradycardia to vagal reflexes arising from the heart itself. Cramer (1915) thought these actions were due to a vagal reflex from the lungs.The pure alkaloid protoveratrine, derived from veratrum album, was studied by Krayer et al. (1944Krayer et al. ( ,1946, renewing clinical interest in the veratrum alkaloids. They reported that the hypotensive effect was due to the presence of ester alkaloids like protoveratrine. They confirmed the work of von Bezold, reporting that the afferent impulses producing the reflex fall in blood pressure arose mainly in the heart, and agreed with Cramer that some afferent impulses were derived from the lungs and suggested that the " carotid sinus area" was concemed, the latter suggestion being supported by the observations of Aviado et al. (1949). Freis et al. (1949), in an investigation of the hmmodynamic effects of the veratrum alkaloids (vertavis and veratrone) in man, reported that the hypotensive effect was due to a decrease in peripheral resistance in the limbs and splanchnic areas without any fall in cardiac output. The decrease in peripheral resistance was apparently caused through the sympathetic nervous system as the drugs did not increase the peripheral blood flow in sympathectomized limbs, whereas they did so in normally innervated limbs. They found that thW alkaloids were not sympatholytic, for pressor reflexes were maintained and postural hypotension-did not occur.Authors using various preparations of mixed veratrum alkaloids in the treatment of hypertension are in agreement that in some patients toxic reactions prevent the administration of effective hypotensive doses. Some authors (Hite, 1946;Freis and Stanton, 1948;Faust, 1951) found these patients to be in a minority, while others (Coe et al., 1950;McNair et al., 1950;Kauntze and Trounce, 1951; Barrow and Sikes, 1951: Smirk and Chapman, 1952) thought they were in a majority. There is general recognition, however, that these alkaloids, were it not for the frequency with which toxic side effects occur, would be suitable therapeutic agents in the treatment of hypertension, since they do not impair sympathetic reflexes or cause marked postural hypertension except in toxic doses. Furthermore, they are effective by mouth, and the effect of a single dose is maintained for several hours; the wide variations in arterial levels that may be produced by ganglion blocking agents such as the methonium compounds are thus avoided.Some clinical observations have been made also with pure veratrum alkaloids. Meilman and Krayer (1950), in a study of the action of protoveratrine given intravenously in man, found that a significant fall of blood pressure could be produced without serious complications. In 1950, Freis e...

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Clinical Studies on Veratrum Alkaloids

Cited by 67 publications

References 4 publications

Asteropsin A: An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2+ influx

Asteropsin A: An unusual cystine-crosslinked peptide from porifera enhances neuronal Ca2+ influx

Medicinal history of North American Veratrum

The Use of the Pure Veratrum Alkaloids Neogermitrine and Protoveratrine in Hypertension

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