The Pharmacology of the Veratrum Alkaloids

Krayer, Otto; Acheson, George H.

doi:10.1152/physrev.1946.26.3.383

Cited by 208 publications

(71 citation statements)

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“…The relative " efficacy " of the anions was C1l<Br-<NO3-<CH3OS03-; this order of potency is similar to that noted by many other workers (see reviews by Horowicz, 1964;Sandow, 1964). Frequently the twitch response was complicated by a " veratrine-like " after contracture (Krayer & Acheson, 1946). Similar activity has been reported by Sandow & Stein (1956) and Liillman (1961) for isolated rabbit and rat skeletal muscle respectively, and the response has been shown to be due to repetitive firing of the muscle (Liullman, 1961).…”

Section: Efjects Of the Anions On Muscle Twitch Responsessupporting

confidence: 82%

The effect of some foreign anions on suxamethonium blockade of the isolated rat diaphragm preparation

Harris

Leach

1970

British J Pharmacology

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Summary1. The pharmacology of suxamethonium blockade of the rat phrenic nervediaphragm preparation has been studied in the presence of some foreign anions. 2. Blockade proceeded in two distinct phases in both normal and modified Krebs solution.3. In normal Krebs solution the characteristics bore no close resemblance to either depolarizing or competitive type blockade. 4. In the presence of foreign anions the characteristics of the blockade more closely resembled those of depolarization. 5. There was an increase in the sensitivity of the motor end-plate region of the muscle to the depolarizing action of acetylcholine, carbachol and suxamethonium in the presence of the anions. 6. Although the anions enhanced the depolarizing activity of suxamethonium, the blocking potency of the drug was unaltered. 7. It is suggested that end-plate depolarization plays little part in suxamethonium blockade of the isolated rat diaphragm and that desensitization is the primary cause of the blockade.

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Section: Efjects Of the Anions On Muscle Twitch Responsessupporting

confidence: 82%

The effect of some foreign anions on suxamethonium blockade of the isolated rat diaphragm preparation

Harris

Leach

1970

British J Pharmacology

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“…It was of interest also to compare the effects of DHO with those of veratrum viride, since the hypotensive action of both drugs is believed to be mediated through the central nervous system (9,34). The two drugs were similar, in that both could decrease arterial pressure and heart rate without depressing cardiac output, they both produced oliguria, and brought about a decrease in renal blood flow during the early, falling phase of the hypotensive response.…”

Section: Discussionmentioning

confidence: 99%

The Hemodynamic Effects of Hypotensive Drugs in Man. Ii. Dihydroergocornine 1

Freis¹,

Stanton²,

Litter³

et al. 1949

J. Clin. Invest.

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Dale in 1906 recognized the sympatholytic activity of crude extracts of ergot as well as their property of direct stimulation of smooth muscle, including that of the blood vessels (1). Despite their sympatholytic effects their direct vasoconstrictor action prevented significant lowering of arterial pressure.Later chemical purification of the crude drug resulted in the isolation of five alkaloids: ergotamine (2), ergobasine (3), ergokryptine, ergocornine and ergocristine (4). The basic chemical structure of these compounds was clarified by Jacobs and Craig (5) who demonstrated the presence of lysergic acid in all of the alkaloids (6). By hydrogenating the reducible double bond of the lysergic acid component of four of these alkaloids, Stoll and Hofmann (7) in 1943 produced a new series of compounds, dihydroergotamine, dihydroergocristine, dihydroergocornine (DHO-180) 5 and dihydroergokryptine (DHK-135).5 Pharmacological studies in animals (8) indicated that these modified compounds have enhanced sympatholytic and adrenolytic properties but little or no direct constrictor action on smooth muscle. In addition, they are hypotensive, this effect being mediated at least in part via the central nervous system (9). In man DHO and DHK in non-toxic doses have sympatholytic and hypotensive prop- erties (10-12). Because of their possible value in the treatment of essential hypertension and peripheral vascular disease a further clarification of their hemodynamic effects in man was undertaken. MATERIALS AND METHODSThe subjects were patients, mostly hypertensive, admitted to the wards of the Massachusetts Memorial Hospitals. The methods used in this investigation were essentially the same as those described in a previous communication (13). DHO was administered by intravenous injection in a solution of sterile water containing 0.5 mg. of active substance per cc. Unless otherwise indicated arterial pressure was measured continuously with a Hamilton manometer (13). RESULTS I. Sympatholytic Effects a. Sympathetic Vasopressor ResponsesCertain vasopressor responses usually abolished or diminished after surgical sympathectomy (14)

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“…It is the relatively low effective dosage range employed in this study which is most apt to show reflex hypotensive action exclusively. 4 The chemical relation to the cardiac glycosides has its parallel in the pharmacologic action upon the mammalian heart. It consists not only in an improvement of contractility of the failing heart by appropriate doses of protoveratrine but in toxic effects by larger doses on impulse conduction and generation of impulses similar to those caused by the cardiac glycosides.…”

Section: Effect Of Erect Posture On Blood Pressure Andmentioning

confidence: 99%

“…In this and subsequent publications the terms "veratrum alkaloids," "veratrum," and "veratrine" will be used in conformity with the suggestions made by Krayer and Acheson. 4 The term "veratrum alkaloids"…”

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confidence: 99%