Anagyrine
Anagyrine is a teratogenic alkaloid first isolated from Anagyris foetida in the year 1885 by French biologists Hardy and Gallois. A. foetida, the Stinking Bean Trefoil, is a highly toxic shrub native to the Mediterranean region, with a long history of use in folk medicine. In the year 1939 Anagyrine was found by James Fitton Couch to be identical to an alkaloid present in many species belonging to the plant genus Lupinus. The toxin can cause crooked calf disease if a cow ingests the plant during certain periods of pregnancy.
Background
The toxicity of certain species of Lupinus plants has been known for several years. The plant is very common in western North America and is sometimes used in feed for cattle if the toxicity of the given lupine is low enough. The toxicity of the plant comes from a variety of toxins, however out of these chemicals anagyrine is the most well known for causing crooked calf disease when ingested by cows. The discovery of anagyrine was made in 1885 by French biologists Ernest Hardy and N. Gallois, who isolated it from the highly toxic legume Anagyris foetida, while the earliest isolation of anagyrine from a lupinus plant was recorded in 1939. The toxin can be found in growing leaf material in a young lupinus plant and in the flower and seed of a mature plant, though varying concentrations of the alkaloid are present throughout lupines that contain anagyrine. It is also found in Thermopsis rhombifolia, though its role in T. rhombifolia toxicity is unknown. The first correlation between anagyrine and crooked calf disease was made by Richard Keeler in 1973. Recently there have been a few successful syntheses of anagyrine recorded, most notably one completed by Diane Gray and Timothy Gallagher.Toxicity
Anagyrine causes crooked calf disease if 1.44 g/kg of the substance is ingested by the mother cow between days 40 and 70 of pregnancy. Out of the hundreds of varieties of lupinus plants, 23 are known to contain high enough concentrations of anagyrine to be dangerous to cattle. The IC50 of anagyrine is 132 μM at Muscarinic [acetylcholine receptor|muscarinic receptors] and 2,096 μM at nicotinic receptors.| Common name | Scientific name |
| Mountain Silvery Lupine | L. alpestris |
| Arctic Lupine | L. arcticus |
| Anderson's Lupine | L. andersonii |
| Spur Lupine | L. arbustus |
| Silvery Lupine | L. argenteus |
| Tail Cup Lupine | L. caudatus |
| unknown | L. cyaneus |
| Lunara Lupine | L. formosus |
| unknown | L. greenei |
| Broad-Leafed Lupine | L. latifolius |
| Spurred Lupine | L. laxiflorus |
| White-Leaved Lupine | L. leucophyllus |
| Nootka Lupine | L. nootaktensis |
| Plumes Lupine | L. onustus |
| Meadow Lupine | L. polyphyllus |
| Rusty Lupine | L. pusillus |
| Silky Lupine | L. sericeus |
| Yellow Lupine | L. sulphureus |
| Burke's Lupine | L. burkei |
| Seashore Lupine | L. littoralis |
| Pine Lupine | L. albicaulis |
| Tall Silvery Lupine | L. erectus |
| Mt. Rose Lupine | L. montigenus |
Symptoms
Known symptoms of crooked cow disease include arthrogryposis, torticollis, scoliosis, kyphosis, and cleft plate. It is thought that teratogenic alkaloids like anagyrine cause the deformities by sedating the fetus, causing it to remain fixed in an abnormal position as it grows. Lasting malformations of the calf can occur even in mild poisonings of the cow because fetal movement depression persists much longer between doses of teratogenic alkaloids than the signs of toxicity in the cow.Symptoms of the alkaloid being ingested by a cow include dyspnea, nervousness, grounding of teeth, depression, salivation, ataxia, spasms, head pressing tremors, seizures, coma, and sometimes death within days of ingestion. If the cattle do not die as a result of alkaloid ingestion, most make a complete recovery with no lasting signs of being poisoned.