Clinical Studies on Veratrum Alkaloids. Iii. The Effect of Protoveratrine on Renal Function in Man 1

Meilman, Edward

doi:10.1172/jci102714

Cited by 31 publications

(20 citation statements)

References 16 publications

(17 reference statements)

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“…In the kidneys, a decrease in renal resistance, due largely to the fall in blood pressure, occurred. Similar observations have been recorded by other investigators employing either Veriloid (9) or Protoveratrine (12). What vasodilatation there was may have been a passive response to the reduced blood pressure since the renal vessels are known to have considerable autonomous capacity to dilate as blood pressure falls.…”

Section: Discussionsupporting

confidence: 85%

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The Effect of Protoveratrine on the Cardiac Output and on Some Regional Circulations in Man 1

Hoobler¹,

Kabza²,

Corley³

1955

J. Clin. Invest.

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Protoveratrine is a mixture of two purified alkaloids derived from veratrum album. According to Meilman and Krayer (1) it has a marked and reproducible depressor effect when given intravenously to hypertensive patients. This effect has been confirmed (2) and the drug has been administered in the long term management of severe hypertension (3). It therefore becomes important to know whether the depressor action of Protoveratrine 3 is a result of a reduction in cardiac output, or of a decrease in total peripheral resistance, and if the latter, what vascular area is chiefly involved. Observations bearing on these questions are presented herewith. METHODSThe Protoveratrine was prepared for intravenous administration according to the method of Meilman

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Section: Discussionsupporting

confidence: 85%

“…Peripheral blood flow was measured by the venous occlusion plethysmograph following the technique outlined by Abramson (7). 1 Supported by grants from Eli Lilly and Co., The National Heart Institute of the U. S. Public Health Service, and the Michigan Heart Association. 2 Present address is 204 Holmcrest Street, Jackson, Michigan.…”

mentioning

confidence: 99%

The Effect of Protoveratrine on the Cardiac Output and on Some Regional Circulations in Man 1

Hoobler¹,

Kabza²,

Corley³

1955

J. Clin. Invest.

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“…Since protoveratrine is eliminated slowly and since its effects are probably a function of the concentration of the drug at the sites of action, continuous intravenous infusions were given to see (1) at what rate elimination proceeds in the human organism, (2) If the size of the initial hypotensive dose is known (see fig. 1 per minute for two minutes, followed by 0.75 pg.…”

Section: Continuous Intravenous Infusionmentioning

confidence: 99%

Clinical Studies on Veratrum Alkaloids

Meilman¹,

Krayer²

1952

Circulation

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An extensive study of the hypotensive properties of protoveratrine, a pure crystalline ester alkaloid from Veratrum album, has been made in hypertensive and normotensive individuals. This drug is shown to be capable of lowering the blood pressure in hypertension of varied etiologies including essential hypertension, acute or chronic renal disease, malignant hypertension, toxemia of pregnancy, and carcinoma of the adrenal cortex. The relationships between dose and response from single intravenous, continuous intravenous, intramuscular and oral administration have been determined.IT WAS SHOWN in a previous communication' that protoveratrine has a hypotensive and cardiodecelerator effect in human hypertension. Although the alkaloid possesses a narrow therapeutic range it may find some application in the therapy of hypertensive disorders. The practical usefulness of a drug, as a tool in the study of human physiology, or as a therapeutic agent, depends upon accurate knowledge of the relation between dose and response. As a rule, this relation varies with the route of administration. Hence, the studies reported earlier were extended to yield information on the influence of the route of administration upon the effect of protoveratrine on blood pressure and heart rate. METHOD

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“…In the clinic, the alternative and complementary medicines, such as "Ji Ming Zi Pills," primarily containing Veratrum alkaloids, were used for the treatment of breast tumor in China. Veratrum alkaloids have also been used clinically for the treatment of hypertension in Chinese hospitals and used medically by Native Americans and Europeans (3)(4)(5)11,(21)(22)(23). Moreover, the marketed veratramine containing medicine "San Qi Xue Shang Ning Capsule" is listed in the Chinese Pharmacopeia (China, 2010) for the treatment of relieving symptoms of blood congestion.…”

Section: Introductionmentioning

confidence: 99%

Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

Lyu

Zhang

Zhou

et al. 2016

AAPS J

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ABSTRACT. Veratramine, a major alkaloid from Veratrum nigrum L., has distinct anti-tumor and antihypertension effects. Our previous study indicated that veratramine had severe toxicity toward male rats. In order to elucidate the underling mechanism, in vivo pharmacokinetic experiments and in vitro mechanistic studies have been conducted. Veratramine was administrated to male and female rats intravenously via the jugular vein at a dose of 50 μg/kg or orally via gavage at 20 mg/kg. As a result, significant pharmacokinetic differences were observed between male and female rats after oral administration with much lower concentrations of veratramine and 7-hydroxyl-veratramine and higher concentrations of veratramine-3-O-sulfate found in the plasma and urine of female rats. The absolute bioavailability of veratramine was 0.9% in female rats and 22.5% in male rats. Further experiments of veratramine on Caco-2 cell monolayer model and in vitro incubation with GI content or rat intestinal subcellular fractions demonstrated that its efficient passive diffusion mediated absorption with minimal intestinal metabolism, suggesting no gender-related difference during its absorption process. When veratramine was incubated with male or female rat liver microsomes/cytosols, significant malepredominant formation of 7-hydroxyl-veratramine and female-predominant formation of veratramine-3-O-sulfate were observed. In conclusion, the significant gender-dependent hepatic metabolism of veratramine could be the major contributor to its gender-dependent pharmacokinetics.

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Clinical Studies on Veratrum Alkaloids. Iii. The Effect of Protoveratrine on Renal Function in Man 1

Cited by 31 publications

References 16 publications

The Effect of Protoveratrine on the Cardiac Output and on Some Regional Circulations in Man 1

The Effect of Protoveratrine on the Cardiac Output and on Some Regional Circulations in Man 1

Clinical Studies on Veratrum Alkaloids

Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

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