Anagyrine is a Teratology alkaloid first isolated from (and named for) Anagyris foetida in the year 1885 by French biologists Hardy and Gallois.[Hardy and Gallois, Comptes-rendus et Mémoires de la Société de Biologie, 13th June 1885] A. foetida (family Fabaceae), the Stinking Bean Trefoil, is a highly toxic shrub native to the Mediterranean region, with a long history of use in folk medicine.[Pedanius Dioscorides, De materia medica Book 3: "Roots of Akanthoda (= Prickly Plants) No. 167 "Anaguris Onaguris"
]
Retrieved at 11.59 on 28/11/22. 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 (lupins).[Couch, James Fitton. "Lupine Studies. XIV.1 The Isolation of Anagyrine FromLupinus Laxiflorusvar.silvicola C. P. Smith." Journal of the American Chemical Society
Retrieved at 12.18 on 28/11/22.
] 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
Lupinus 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 (born Paris 1826) 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.
[Hardy, E., and N. Gallois. "Keeler, Richard F. "Lupin Alkaloids from Teratogenic and Nonteratogenic Lupins. I. Correlation of Crooked Calf Disease Incidence with Alkaloid Distribution Determined by Gas Chromatography." Teratology 7.1 (1973): 23-30. Wiley Online Library. Web." The Journal of the Chemical Society 54 (1888): n. pag. Abstract. The Journal of the Chemical Society (n.d.): n. pag. Print.] 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.
[Keeler, Richard F. "Lupin Alkaloids from Teratogenic and Nonteratogenic Lupins. I. Correlation of Crooked Calf Disease Incidence with Alkaloid Distribution Determined by Gas Chromatography." Teratology 7.1 (1973): 23-30. Wiley Online Library. Web.] Recently there have been a few successful syntheses of anagyrine recorded, most notably one completed by Diane Gray and Timothy Gallagher.
[Gray, Diane, and Timothy Gallagher. "A Flexible Strategy for the Synthesis of Tri- and Tetracyclic Lupin Alkaloids: Synthesis of ( )-Cytisine, (±)-Anagyrine, and (±)-Thermopsine." Angewandte Chemie International Edition 45.15 (2006): 2419-423. Web.]
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 (listed below) are known to contain high enough concentrations of anagyrine to be dangerous to cattle.
[Davis, A. M., and D. M. Stout. "Anagyrine in Western American Lupines." Journal of Range Management 1.39 (1986): n. pag. Web. 23 Apr. 2017.][Gupta, Ramesh C. Veterinary Toxicology: Basic and Clinical Principles. N.p.: Academic, 2007. Print.] The IC
50 of anagyrine is 132 μM at muscarinic receptors and 2,096 μM at nicotinic receptors.
Symptoms
Known symptoms of crooked cow disease include
arthrogryposis (permanently flexed joints),
torticollis (twisting of the neck),
scoliosis (curving of the spine),
kyphosis (humpback), 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.
["AAHP Field Disease Investigation Unit (FDIU)." Crooked Calf. Washington State University: College of Veterinary Medicine, 2015. Web. 23 Apr. 2017.] Lasting malformations of the calf can occur even in mild poisonings of the cow because fetal movement depression persists much longer between doses of
Teratogen 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, 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.[Schenck, Patricia. Saunders Comprehensive Review of the Navle: Pageburst Retail. Place of Publication Not Identified: Elsevier Saunders, 2009. Print.][GUPTA, RAMESH C. Reproductive and Developmental Toxicology. Place of Publication Not Identified: ELSEVIER ACADEMIC, 2017. Print.]
Mechanism of Action
While the specific mechanism of action of anagyrine is unknown, the structure of anagyrine allows it to be mistaken for
acetylcholine by certain receptors in living organisms. Anagyrine is thought to act as an acetylcholine agonist, increasing the amount of signal being sent to muscles in the organism's body, much like
nicotine. Anagyrine interacts with nicotinic and muscarinic acetylcholine receptors, however it binds to muscarinic receptors 16 times more strongly, making it likely that the blocking of muscarinic acetylcholine receptors is what causes crooked calf disease.
Further reading
