Calotropin

Emergency treatment: Plants- cardiac glycosides; [HSDB] Intraperitoneal LD50 (mouse) = 9800 ug/kg; Causes ataxia, somnolence, and seizures at lethal doses; [RTECS] Milkweed (Asclepias spp) contains cardiac glycosides; [Olson, p. 385] Milkweed (Asclepias spp) contains cardenolides that are cardiac toxins; [Goldfrank, p. 1538] See Calotoxin.

CALOTROPIS PROCERA, A SHRUB NATIVE TO AFRICA, WAS THE FIRST SOURCE FOR ISOLATION OF THE CYCLIC BRIDGED GLYCOSIDES. FROM CALOTROPIS LATEX...WERE SEPARATED CALOTROPIN, CALACTIN, CALOTOXIN, USCHARIDIN, USCHARIN AND VORUSCHARIN -A NEW SERIES OF CARDENOLIDES WITH A COMMON GENIN, CALOTROPAGENIN.

MILKWEED POISONING IN SHEEP AND CATTLE REMAINS A PROBLEM TO RANCHERS, PARTICULARLY WHEN ADEQUATE QUANTITIES OF POTABLE FORAGE ARE UNAVAILABLE OR WHEN MILKWEEDS ARE INCORPORATED IN CUT FEED. ... NERVOUS & GASTROINTESTINAL SYMPTOMS INCLUDE DEPRESSION AND APATHY, WEAKNESS, LOSS OF MUSCLE CONTROL, FALLING, DILATED PUPILS, RESPIRATORY PARALYSIS, INTESTINAL STASIS AND FERMENTATION, AND OCCASIONALLY, DIARRHEA. SOMETIMES TETANIC SEIZURES ARE SEEN. ...SYMPTOMS MAY BEGIN AS EARLY AS 2 HR AFTER INGESTION OF THE PLANT & MAY CONTINUE FOR HR OR DAYS. A POISONED ANIMAL MAY OR MAY NOT EXPERIENCE A PERIOD OF COMA BEFORE DYING. LESIONS AT DEATH INCLUDE ACUTE CATARRHAL GASTROENTERITIS AND CONGESTION OF THE LUNGS & SOMETIMES OF THE KIDNEYS. /MILKWEED POISONING/

...(LD50) OF...CALOTROPIN FROM ASCLEPIAS CURASSAVICA (A MILKWEED ALSO KNOWN FOR ITS TOXICITY TO CATTLE), WERE DETERMINED USING MALE SWISS WEBSTER MICE /9.2 MG/KG INTRAPERITONEAL/. ... AFFECTED ANIMALS BECAME QUIET & ATAXIC. RESPIRATION BECAME RAPID BUT LABORED, AND ANIMALS LAID FLAT ON THEIR ABDOMENS WITH THEIR LIMBS SPREAD. THERE WAS SOME TREMBLING, AND SEVERELY AFFECTED ANIMALS CONVULSED. SYMPTOMS APPEARED WITHIN A FEW MINUTES AFTER THE MICE WERE DOSED; AND DEATH, ACCOMPANIED BY CLONIC CONVULSIONS, USUALLY OCCURRED WITHIN 1-2 HR. MICE THAT EXHIBITED SYMPTOMS OF POISONING, BUT SURVIVED, DID NOT APPEAR ILL ON THE DAYS FOLLOWING TREATMENT. NO LESIONS WERE CLEARLY VISIBLE IN MICE THAT DIED WITHIN 24 HR OF BEING DOSED. HEMORRHAGES WERE SEEN IN THE LUNGS OF ANIMALS EUTHANIZED ON THE DAYS FOLLOWING TREATMENT, BUT THE INCIDENCE OF THIS LESION WAS NOT SIGNIFICANTLY GREATER THAN THE INCIDENCE IN THE CONTROL GROUP.

(NA+,K+)-ATPASE PRESENT IN CARDIAC MUSCLE HAS BEEN PROPOSED AS THE PHARMACOLOGICAL RECEPTOR FOR CARDIAC GLYCOSIDES. INHIBITION OF THIS ENZYME SYSTEM IS THOUGHT TO BE RESPONSIBLE FOR THE THERAPEUTIC OR TOXIC EFFECTS OF CARDIAC GLYCOSIDES ON THE HEART OF VERTEBRATES. THE ABILITY OF NATURAL AND SEMISYNTHETIC CARDIAC GLYCOSIDES TO INHIBIT (NA+,K+)-ATPASE PREPARATIONS HAS BEEN USED TO PREDICT THE EXTENT OF THEIR EFFECT ON THE MYOCARDIUM. ... THE EVIDENCE CITED...INDICATES THAT ALL CARDENOLIDES MAY BE REGARDED AS HIGHLY TOXIC, THAT SENSITIVITY TO CARDENOLIDES MAY VARY CONSIDERABLY AMONG SPECIES AND THAT THE PRINCIPAL TOXIC EFFECTS ARE ASSOCIATED WITH THE MYOCARDIUM.

EARLY STUDIES ON CARDENOLIDE SEQUESTRATION FROM MILKWEEDS WERE CARRIED OUT WITH THE GRASSHOPPER, POEKILOCERUS BUFONIUS. THIS APOSEMATIC NORTH AFRICAN SPECIES, WHICH PROBABLY FEEDS EXCLUSIVELY UPON MILKWEEDS IN NATURE, HAS A POISON GLAND FROM WHICH THE CONTENTS MAY BE EJECTED AS SPRAY DURING THE IMMATURE HOPPER STAGE, OR AS A FOAMY FROTH IN THE ADULT STAGE. THE SECRETION CONTAINS HISTAMINE AND ONE CAT-LETHAL DOSE OF CARDENOLIDE. WHEN REARED ON CALOTROPIS PROCERA OR ASCLEPIAS CURASSAVICA, THE GRASSHOPPERS SECRETION CONTAINED ONLY CALACTIN AND CALOTROPIN IN APPRECIABLE QUANTITIES OF THE SEVEN OR SO RELATED CARDENOLIDES PRESENT IN THE PLANT.

SELECTIVE STORAGE OF SOME CARDENOLIDES FROM AMONG SEVERAL IN THE FOOD PLANT WAS CONFIRMED /IN MONARCH LARVAE/... THAT METABOLIC CONVERSION MIGHT BE INVOLVED IN THIS SELECTIVITY WAS PROVEN BY SEPARATE ADMIN OF GRADED DOSES OF INDIVIDUAL CARDENOLIDES TO MONARCH LARVAE, WITH SUBSEQUENT ANALYSIS OF THE CARDENOLIDE CONTENT OF THE LARVAE & ADULTS. CALACTIN & CALOTROPIN WERE STORED INTACT, BUT USCHARIDIN WAS METABOLIZED TO A MIXTURE OF CALACTIN & CALOTROPIN, WHICH WERE THE CARDENOLIDES STORED. THIS CONVERSION, A REDUCTION, OCCURRED VERY RAPIDLY DURING FEEDING, APPARENTLY IN THE GUT. REASONS OFFERED FOR THE STOREABILITY OF CALACTIN & CALOTROPIN, BUT NOT USCHARIDIN, INCL CHEMICAL INSTABILITY OF THE LATTER IN THE GUT MILIEU, POLARITY (CALACTIN & CALOTROPIN ARE MORE POLAR THAN USCHARIDIN), & THE POSSIBILITY THAT THE C-3'OH IN THE CALACTIN & CALOTROPIN WAS NEEDED FOR BINDING TO A CARRIER AND/OR TISSUE STORAGE SITE.