Toxicity of Palicourea marcgravii: combined effects of fluoroacetate, N-methyltyramine and 2-methyltetrahydro-beta-carboline.
Feeding experiments carried out with cattle and horses could prove the toxic effects of P. marcgravii (Rubiaceae) in all cases. The typical symptoms of "sudden death", however, are observed in ruminants only. This difference could not be explained so far. Apart from fluoroacetate, two more substances also have influence the toxic effects and have been isolated from P. marcgravii for the first time: N-methyltyramine and 2-methyltetrahydro-beta-carboline (2-Me THBC). Structure elucidation of these compounds is mainly accomplished by 1H-NMR, 13C-NMR and MS techniques. Due to the small quantity of fluoroacetate (5.4 micrograms/g plant), the main toxic effect obviously lies in the two discovered substances. In contrast to the slow death of horses (monogastriers), the "sudden death syndrome" of cattle (ruminants) can be explained as a result of the higher resorbility of these two substances in the gastro-intestinal system. Given orally, both substances influence the monoamine oxidase type A (MAO-A): N-methyltyramine acts as a competitive substrate, and 2-Me THBC is one of the most effective MAO-A-inhibitors. Thus, the decomposition of the specific MAO-A-substrates noradrenaline and adrenaline as well as of N-methyltyramine itself is inhibited. The alpha- and beta-receptors of the sympathetic system are stimulated more strongly, which leads to a drastic rise in blood pressure and thereby to a more rapid distribution of fluoroacetate in the body. This results in a reinforced input of fluoroacetate in the cells of especially active organs of the body (heart etc.). Thus, even smaller quantities of fluoroacetate are lethal.
Kemmerling
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Chemisches Institut der Tierärztlichen Hochschule Hannover, Bundesrepublik Deutschland.
D000821:Animal Feed; D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D002417:Cattle; D002418:Cattle Diseases; D003645:Death, Sudden / Q000662:veterinary; D005463:Fluoroacetates / Q000302:isolation & purification / Q000633:toxicity*; D005517:Foodborne Diseases / Q000401:mortality / Q000662:veterinary; D006734:Horse Diseases; D006736:Horses; D013058:Mass Spectrometry; D015394:Molecular Structure; D018515:Plant Leaves; D010947:Plants, Toxic / Q000737:chemistry; D014439:Tyramine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity
D002243:Carbolines; D005463:Fluoroacetates; C009777:2-methyltryptoline; C014815:fluoroacetic acid; C036244:methyl-4-tyramine; D014439:Tyramine