Veratrine

Veratrine, Veratrinum, a white powder, without odor, strongly irritating to mucous membranes, of acrid-burning taste, difficult to dissolve in water, of alkaline reaction, amorphous (however, under the microscope crystals can be found in it). Extremely poisonous. It was first obtained in 1818 by Meissner from the seeds of Sabadilla officinalis, and in 1819 by Pelletier and Caventou from the rhizome of Veratrum album. The amorphous alkaloid of supposed composition C32H49NO9, obtained in 1879 by Wright and Luff from the seeds of Sabadillae officinalis, was also named V. To distinguish from each other the various alkaloids bearing the same name V., Schmidt named Meissner's V. official - Veratrinum officinale, proving at the same time that the named preparation consists of a mixture of two isomeric alkaloids having the empirical formula C₃₂H₄₉NO₉: 1) "crystalline V.", or cevadine (Cevadinum), almost insoluble in water, decomposing into cevine base and angelic acid, and 2) non-crystalline but water-soluble veratridine (i.e. "water-soluble V."), decomposing with the formation of veratric acid veratroine. Official V. is not found in Veratrum album. Different V. act on the animal organism differently; the data below refer to pure "crystalline veratrine", or cevadine (Lissauer). Even in very small doses cevadine irritates the endings of sensory and secretory nerves of the mucous membranes of the nose, mouth, eyes, respiratory tract, stomach and intestines, which in such cases causes incessant sneezing, profuse salivation, lacrimation, cough, stabbing pains in the stomach and intestines, nausea, vomiting and often diarrhea. Since cevadine subsequently paralyzes the endings of sensory nerves, all the above-mentioned irritation phenomena disappear. In frogs, cevadine, when administered subcutaneously, causes increased secretion of skin secretions. Since cevadine does not cause hyperemia of the skin when acting on it, the action of cevadine on sensory nerves is considered particularly specific. On the endings of motor nerves in striated muscles, cevadine acts (Boehm), like curare, paralytically. On the central nervous system, cevadine exerts the following influence: respiration changes (slows down, becomes intermittent and may completely stop from paralysis of the respiratory center), circulation is disturbed (the vasomotor center is depressed to paralysis; blood pressure falls), vagus nerves are paralyzed, ataxia, convulsions and spasms appear; vomiting movements. But the action of cevadine on striated muscles is especially characteristic. In small doses, cevadine increases the contractile ability of muscles, increases their extensibility and increases their performance. With toxic doses of cevadine, the above phenomena can also be observed, but for a short time, after which the muscles become easily fatigable, their performance drops sharply, and the muscles soon become paralyzed. Such toxic action from cevadine causes in a poisoned frog sharp changes in the nature of its movements: after a jump, the hind legs of the frog remain extended for some time, after which the animal pulls them in and bends them one by one; later the frog no longer jumps, but crawls clumsily, and in its muscles rigidity and fibrillary twitching can be determined. The myographic curve obtained in this case differs by an unusually long descending part, approximately 30-60 times longer than that of a normal muscle. Thus, it is proved that the relaxation of skeletal muscles from cevadine is sharply slowed down. On myographic curves from cevadine, so-called two-peaked curves of muscle contraction can often be seen with single stimulation, which indicates (Mostinsky) a lesser degree of poisoning from cevadine. On the cardiac muscle, cevadine acts in a similar way (Boehm): systole proceeds more energetically, diastolic relaxation becomes less complete; heartbeats slow down, peristalsis sets in, then the ventricle stops in systole, while the atria continue to pulse but gradually all slower; finally, their contractions also fade. The stoppage in systole of an isolated rabbit heart can from V. (Kulyabko) last for several minutes, and then pulsations first appear in the atrium, and later in the ventricles. By washing, almost complete restoration of normal heart activity can be achieved. Compared to other cardiac poisons, cevadine acts on the heart relatively weakly (Boehm). From a biological point of view, the observations of Korenchevsky are interesting that V. acts on the contractile elements of infusoria and paramecia, in general, the same as on the muscles of higher animals; also important are the indications of Fiirth that cevadin promotes the clotting of myogen and myosin. Cevadine is quickly absorbed and excreted from the animal body with urine. With therapeutic internal use of V., even from very small doses (0.003), poisoning can occur in the patient: dizziness, darkening of the eyes, irregular pulse, salivation, nausea, vomiting, pain in the stomach and intestines, diarrhea, general weakness, pallor and coldness of the skin, fall in temperature, difficulty breathing, cyanosis, convulsions, collapse and death. Help in case of poisoning: wash the stomach and intestines with a 0.2% solution of tannin, give caffeine, strong wine internally; for colics - opium, morphine, cocaine; under the skin - ether, camphor; artificial respiration; if V. got on the mucous membranes of the nose or eyes, lubricate them with a 3% solution of hydrochloric cocaine. Official V. (Ph VII) is used in the form of a 1-3% ointment or 1-5% alcoholic solution for neuralgic and rheumatic pains. Internally and subcutaneously V. is no longer used due to its poisonousness.

V. Nikolaev. Discovery of V. in judicial cases. Poisonings from V. are not frequent. When examining internal organs, vomit, etc. for alkaloids (see Poisons), V. passes into chloroform from an alkaline solution. The chloroform extract is evaporated at a temperature of 15-18°. Concentrated sulfuric acid first gives it a yellow coloration, turning into orange, red, then after 1/4-1 hour into carmine-red. Concentrated hydrochloric acid causes a beautiful red coloration when heated, very constant. Products of protein decomposition repeatedly gave the same color reactions, therefore pharmacological testing for veratrine is also necessary.