Published March 13, 1986; Replaced April 15, 1994.
List of German Commission E Monographs (Phytotherapy)
Ammeos visnagae fructus; ammi visnaga berries, bishop's weed.
Bishop's weed berries, consisting of the dried ripened berries of Ammi visnaga (L.) Lamarck [syn. A. daucoides Gaertn.] [Fam. Apiaceae], as well as pharmaceutical preparations of same.
The results of pharmacological, pharmacokinetic and toxicological research on one have focused on a dry extract of bishop's weed berries corresponding to 10.5 percent gamma pyrones calculated as khellin (extraction medium: methanol/water 70 - 30, 70 - 99 percent natural extract, drug-extract ratio = 6.2:10.1).
In the modified Langendorff heart preparation for the guinea pig, a slight (8.8 percent) and brief increase of the coronary perfusion (starting with a concentration of 20 ¬Ķ/ml) was observed to occur within the first 10 minutes.
In rats an increase of the heart minute volume occurs after an infusion of the extract of 1 mg/kg of body weight x min; the effect lasts for about an hour after the infusion has been discontinued.
The heartbeat of rats increases significantly after a 30-minute infusion of 1 mg/kg body weight x min.
KCl - or noradrenalin-induced spasms in the aorta of guinea pigs are relaxed by the extract as well as by the substances khellin, visnadin and visnagin in micromolar concentration in the extract. The extract at its highest concentration (316 ¬Ķg/ml ) causes a 46.3 percent reduction in the K+ spasms and a 64.9 percent reduction in the noradrenalin induced spasms.
After oral administration of 140 mg extract, khellin and visnadin were found in the plasma of six of the test subjects. No traces of visnagin were found; the maximum concentration of khellin was reached between 20 and 60 minutes at 29.4 and 276.5 ng/ml. Elimination occurred quickly; after 10 hours khellin was no longer detectable. For khellin the mean value was Cmax value of 98.3 ng/ml. The LD50 of the extract administered orally is greater than 2000 mg/kg body weight for rats and mice.
After dosing rats with 10, 150 and 6000 mg extract/kg body weight over a period of four weeks, a minimal toxic level was reached at between 10 and 150 mg. After a 600 mg dose had been administered a mild to medium grade centrolobular hypertrophy of the liver parenchym with hepatocellular degeneration occurred.
There are no studies available on chronic toxicity, carcinogenicity, mutagenicity or teratogenicity.
Clinical Data 1. Uses Indications established through research Claimed areas of use and explanation of rejection. Preparations of Bishop's Weed berries are used in the treatment of angina pectoris, coronary insufficiency, paroxsysmal tachycardia, extra systoles, presbycardia with hypertonia, asthma, whooping cough and cramp-like complaints of the abdomen. In combination preparations Bishop's Weed berries are used as secondary treatments of early aging in the area of the heart and the circulatory and vascular systems, after cardiac arrest, in nervous complaints of the heart, hypertonia; in bronchitis, bronchial asthma and coughs; spasms of the gastrointestinal tract, gallbladder and urinary tract; in disorders of the hepatobiliary system, kidney stones, tendency to form stones after surgery, kidney insufficiency, in the reduction of hormone-based ureter dilation in the second and third trimesters of pregnancy and on taking contraceptives; as a secondary antibacterial treatment of acute and chronic pyelonephritis in therapy-resistant cases; in climacteric complaints, depressions and in the prevention of hardening of the arteries and accompanying symptoms. The efficacy of the drug in the above-named areas has not been sufficiently proven. (Only one therapeutic observation has been reported.)
In rare cases pseudoallergic reactions, reversible cholostatic icterus/jaundice.
The khellin contained in the drug sensitizes the skin to light. For the duration of the treatment, therefore, long periods of exposure to the sun and concentrated ultraviolet radiation should be avoided.
After higher doses of khellin (100 mg daily administered orally), increased activity of the liver transaminases and of the gamma-glutamyltransferase have been observed.
Due to the insufficiently proven efficacy of the drug and its pharmaceutical preparations, as well as the associated risks, therapeutic use cannot be recommended.
How effective any spasmolytic action of the drug is when used in fixed preparations must be tested and proven for each individual preparation.
Ed. note: This monograph was originally published on March 13, 1986, as appoved. Due to new information on potential risks, its status changed to unapproved on April 15, 1994.]. -->