€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF PHYSIOLOGY***** Thames MD Peterson MG Schmid PG Stimulation of cardiac receptors with veratrum alkaloids inhibits ADH secretion. In: Am J Physiol (1980 Dec) 239(6):H784-8 ISSN: 0002-9513 The purpose of this study was to determine whether cardiac receptors that are stimulated by veratrum alkaloids exert an inhibitory influence on the secretion of vasopressin (ADH). In six chloralose- anesthetized dogs, injection of cryptenamine (2 microgram/kg) into the circumflex coronary artery resulted in a significant (P < 0.05) fall in arterial pressure (-45 +/- 5 mmHg). Despite this hypotension and the presence of intact arterial baroreflexes, there was no change in plasma ADH (measured in the superior vena cava). In eight dogs with sinoaortic baroreceptor denervation, hemorrhage of 10 ml/kg decreased arterial pressure 20 +/- 5 mmHg (P < 0.05) and increased plasma ADH from 14 +/- 5 to 38 +/- 13 microU/ml (P < 0.05). Intracoronary injection of cryptenamine (1 microgram/kg) decreased plasma ADH to 23 +/- 7 microU/ml during the 5 min immediately after cryptenamine injection and to 16 +/- 4 microU/ml 20 min after injection. In eight dogs with sinoaortic denervation, hemorrhage and injection of vehicle resulted in a progressive increase in plasma ADH over the same time period. Vagotomy abolished the inhibitory response to cryptenamine injection. These data show that stimulation of cardiac receptors with vagal afferents by intracoronary injection of a veratrum alkaloid inhibits ADH secretion. Activation of these receptors can prevent arterial baroreflex-induced increases in ADH. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hasser EM DiCarlo SE Applegate RJ Bishop VS Osmotically released vasopressin augments cardiopulmonary reflex inhibition of the circulation. In: Am J Physiol (1988 May) 254(5 Pt 2):R815-20 ISSN: 0002-9513 Exogenous arginine vasopressin (AVP) has been shown to augment the inhibitory influence of arterial and cardiopulmonary baroreflexes. This study examined the influence of osmotically released AVP on the inhibitory responses to activation of cardiopulmonary receptors by administration of veratrum alkaloids. Three groups of conscious dogs, with carotid sinus intact, with prior sinoaortic denervation (SAD), and with prior lesion of the area postrema (AP), were instrumented for monitoring arterial pressure and heart rate and with left circumflex coronary artery or left atrial catheters for administration of veratrum alkaloids. Conscious dogs were administered veratridine (0.5-1.0 microgram.kg-1.min-1) under control conditions, after infusion of hypertonic saline (HS, 6% NaCl), and after HS in the presence of the AVP vascular (V1) receptor antagonist. In carotid sinus-intact dogs, veratridine reduced arterial pressure (-10 +/- 0.4 mmHg). After HS infusion, the depressor response to veratridine was significantly greater (-18 +/- 0.8 mmHg). The enhanced depressor response during HS infusion was prevented by administration of the AVP antagonist (-8 +/- 0.6 mmHg). Responses to veratrum alkaloids in SAD dogs were similar. In AP- lesioned animals, the depressor effects of veratridine (-9 +/- 0.5 mmHg) were similar to intact animals. However, the response to veratridine during HS was not altered (-9 +/- 0.8 mmHg) in AP- lesioned dogs. Results suggest that osmotically stimulated AVP augments the inhibitory effects of cardiopulmonary reflexes and that this effect is mediated through the area postrema via the V1 receptor. Registry Numbers: 113-79-1 (Argipressin) 71-62-5 (Veratridine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CLINICAL OBSTETRICS AND GYNECOLOGY***** Kelly JV Drugs used in the management of toxemia of pregnancy. In: Clin Obstet Gynecol (1977 Jun) 20(2):395-410 ISSN: 0009-9201 Drugs used in the management of pregnancy-induced hypertension have been reviewed, and their value and adverse effects on both mother and fetus have been considered. Although magnesium and hydralazine remain the stalwarts of therapy, a number of other drugs have potential that may be realized in the future. Several new medications have promise in correcting the derangements of toxemia, but safety for the fetus has yet to be demonstrated. For the physician confronted with the complexities of old and new drugs in toxemia of pregnancy, the prayer of Lord Berkely may be just as appropriate in 1977 as it was dicades ago: From inability to let well enough alone, From too much zeal for the new, From too much contempt for what is old, From putting knowledge before wisdom and science before art, From making the cure of the disease more grievous than its endurnace, Good Lord, deliver us. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FEDERATION PROCEEDINGS***** Hintze TH Reflex regulation of the circulation after stimulation of cardiac receptors by prostaglandins. In: Fed Proc (1987 Jan) 46(1):73-80 ISSN: 0014-9446 Prostaglandins (PGs) are potent vasoactive substances that may participate in the control of coronary blood flow, platelet aggregation, and inflammation. An important action of PGs may be the stimulation of c fibers in general and vagal cardiac c fibers in particular. The Bezold-Jarisch reflex after intracoronary injection of Veratrum alkaloids is very similar to the vagal bradycardia elicited by stimulation of cardiac PG synthesis or injection of prostacyclin (PGI2). The characteristic features of this reflex are 1) stimulation of c fibers, 2) inferoposterior wall location of receptors, 3) vagal afferents, 4) vagal efferents to the heart, 5) sympathetic efferents to peripheral blood vessels, and 6) interaction with other reflexes. Vagal cardiac c fibers are activated by intracoronary injections of PGI2 or arachidonic acid, resulting in a vagal reflex bradycardia and hypotension due to withdrawal of peripheral alpha-adrenergic tone to resistance vessels. The cardiac receptors are located predominantly in the inferoposterior wall of the left ventricle. When stimulated by PGs, cardiac receptors may also modify the regulation of arterial pressure by the baroreflexes, altering the inverse relationship between systemic arterial pressure and heart rate. Thus, there is a striking parallelism between the veratridine-induced Bezold-Jarisch reflex and PG-induced cardiac reflexes, although the physiological and clinical significance of these reflexes remains to be determined. Registry Numbers: 506-32-1 (Arachidonic Acid) 71-62-5 (Veratridine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF NEUROCHEMISTRY***** Milligan G Strange PG Muscarinic acetylcholine receptors in neuroblastoma cells: lack of effect of Veratrum alkaloids on receptor number. In: J Neurochem (1984 Jul) 43(1):33-41 ISSN: 0022-3042 The effect of compounds that activate sodium channels on the number of muscarinic acetylcholine receptors in neuroblastoma NIE 115 cells has been investigated. The cells were used in electrically unexcitable ("control" cells) and excitable ("differentiated" cells) states. Although receptor assays using a single concentration of the radioligand [3H]scopolamine methyl chloride indicated a loss of receptors after a 6-h incubation of cells with veratrine, no true loss of receptors was seen with any of the compounds tested (veratridine, veratrine, aconitine) when full saturation analyses were performed in either control or differentiated cells. The apparent receptor loss seen with veratrine was due to a muscarinic receptor-active component of veratrine (not veratridine) occluded by the cells and released into the binding assays upon cell breakage. Veratridine and aconitine have a very low affinity for muscarinic acetylcholine receptors, and the binding of carbamoylcholine to the receptors is unaffected by tetrodotoxin, so that there is no evidence in this system for interaction between muscarinic receptors and sodium channels. Registry Numbers: 13265-10-6 (N-methylscopolamine) 302-27-2 (Aconitine) 62-59-9 (Veratrine) 71-62-5 (Veratridine) 7440-23-5 (Sodium) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF TOXICOLOGY. CLINICAL TOXICOLOGY***** Fogh A Kulling P Wickstrom E Veratrum alkaloids in sneezing-powder a potential danger. In: J Toxicol Clin Toxicol (1983 Apr) 20(2):175-9 ISSN: 0731-3810 Sneezing-powders containing pulverized root of veratrum album (white hellebore) have recently been marketed in the Scandinavian countries. The powder, imported from the Federal Republic of Germany, has caused severe intoxications. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF CHINESE MEDICINE***** Petkov V Plants and hypotensive, antiatheromatous and coronarodilatating action. In: Am J Chin Med (1979 Autumn) 7(3):197-236 ISSN: 0192-415X However great the success in the therapy of hypertension, atherosclerosis and ischemic heart disease has been gained today by recent efficient drugs, the definite healing of patients is not yet attained. The late discovery of reserpine, such an efficient drug of plant origin against hypertension, convinced so far reluctant scientists to consider the chemical compounds of the plant world. With respect to this traditional medical knowledge, it seems necessary to define more accurately the specificity of these healings- sometimes recommended unspecifically for a whole branch of medicine. This experimental verification should not use inconsiderately the present-day classification of diseases; there should be an awareness that conventional experimental methods in pharmacology are often unsuitable for revealing the real biological activity of one or another medicinal plant. The interest in the millennial empirical field of health care is acknowledged by the World Health Organization which promotes research and development of traditional medicine, along with investigations into its psychosocial and ethnographic aspects. These studies cover a number of plants growing in Bulgaria that have a healing effect in hypertension, atherosclerosis and ischemic heart disease according to the data of traditional medicine. Using screening methods, extracts and chemically pure substances were investigated; extraction was done with solvents such as water, ether, chloroform, dichloretan, ethanol, methanol, and acetone. Most of the experiments were carried out on anesthetized cats, rabbits and dogs. The substances tested were applied mainly intravenously, and in some experiments orally. Chronic experiments were also carried out on wakeful dogs with induced hypertension, on animals fed on an atherogenic diet, and on animals with induced arrhythmia and coronary spasm. Data are presented of clinical examination of some plants or of active substances isolated from them. Major results of these studies are presented for the following plants: Garlic, Geranium; Hellebore; Mistletoe; Olive; Valerian; Hawthorn; Pseucedanum arenarium; Periwinkle; Fumitory. For another 50 plants growing in Bulgaria and in other countries the author presents his and other investigators' experimental and clinical data about hypotensive, antiatheromatous and coronarodilatating action. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANNALES DE MEDECINE INTERNE***** Garnier R Carlier P Hoffelt J Savidan A [Acute dietary poisoning by white hellebore (Veratrum album L.). Clinical and analytical data. A propos of 5 cases] Intoxication aigue alimentaire par l'ellebore blanc (Veratum album L.). Donnees cliniques et analytiques. A propos de 5 cas. In: Ann Med Interne (Paris) (1985) 136(2):125-8 ISSN: 0003-410X (Published in French) Five cases of acute accidental poisoning with White Hellebore are reported. All cases occurred several minutes after the ingestion of home-made gentian wine. The clinical signs were nausea, vomiting, abdominal pain, hypotension and bradycardia. The initial ECG showed sinus bradycardia in 4 cases. In one patient, complete atrioventricular block with an ectopic atrial bradycardia and an intermittent idioventricular rhythm was recorded. Symptomatic treatment and/or atropine led to recovery within a few hours. These symptoms suggested poisoning with a veratrum alkaloid. The White Hellebore (Veratrum Album L.) and the Yellow Gentian (Gentiana Lutea L.) often grow side by side in the fields; it is easy to confuse the two plants before they flower if one is not a botanist. Each gentian wine was analysed by thin layer chromatography and chemical ionisation spectrometry. All the wines contained Veratrum alkaloids. Registry Numbers: 51-55-8 (Atropine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****BRAIN RESEARCH BULLETIN***** Van Huizen F Wilkinson M Cynader M Shaw C Sodium channel toxins veratrine and veratridine modify opioid and muscarinic but not beta-adrenergic binding sites in brain slices. In: Brain Res Bull (1988 Jul) 21(1):129-32 ISSN: 0361-9230 We have examined the influence of the sodium channel toxins veratrine and veratridine on mu-opioid ([3H]-DAGO), muscarinic ([3H] NMS) and beta-adrenergic ([3H] CGP) receptors in rat brain slices. These drugs reduce opioid and muscarinic binding while leaving beta-receptors unaffected. Veratrine is inhibitory at 0 degree or at 30 degrees C whereas veratridine is without effect at 0 degree C. These data suggest that some factor contained in the mixture of drugs (veratrine) can block opioid and muscarinic receptors independently of depolarization. Veratridine does not affect muscarinic receptors at ice temperature. Similar observations were made in thin sections of cat brain at 0 degree C. The concentrations of the toxins which cause 50% inhibition of binding are well within the range (5 x 10(-5) M-10(-4) M) routinely used for depolarization experiments. We suggest that caution be used in the interpretation of results obtained from veratrum alkaloid-induced depolarizations. It would not be surprising if the binding of other ligands to their receptors was also affected. Registry Numbers: 62-59-9 (Veratrine) 71-62-5 (Veratridine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY***** Brizzee KR Mechanics of vomiting: a minireview. In: Can J Physiol Pharmacol (1990 Feb) 68(2):221-9 ISSN: 0008-4212 In a cineradiographic analysis of the vomiting reflex in response to i.v. administration of an emetic drug (lanatoside C, 12 mg/kg) in cats, it was shown that the vomiting act is preceded by cyclic periods of abnormal peristaltic activity of the small bowel and inhibition of gastric peristalsis. It was further observed that massive antiperistalsis of the upper small bowel with reflux into the stomach is a common occurrence in the period immediately preceding vomiting. The emetic act itself is composed of phases of esophageal dilation, gastric emptying, gastric reflux, and esophageal collapse in cyclic repetition. The response of the esophagus and the stomach during emesis is passive, with external pressures and forces apparently providing the expulsive forces, the gastric bolus being contained by contraction of the pylorus and probably an upper esophageal or pharyngeal barrier. Earlier studies were conducted in cats in which observations were made on changes in thoracic venous pressure, abdominal venous pressure, and arterial blood pressure associated with vomiting induced by Veratrum alkaloids. Retching was characterized by a growing series of brief negative intrathoracic pressure pulses mirrored by positive pressure pulses in the abdomen. Expulsion then occurred and was followed with a sudden reversal of intrathoracic pressure from negative to positive. Expulsion involved a more sustained abdominal contraction, but both retching and expulsion were brought about by the same set of muscles, according to their EMG profiles. From results observed following phrenicotomy and spinal cord section at T5, it was concluded that the diaphragm, acting together with the inspiratory muscles against a closed glotis is responsible for the negative intrathoracic pressure that occurs in retching.(ABSTRACT TRUNCATED AT 250 WORDS) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CESKA A SLOVENSKA FARMACIE***** Grancai D Grancaiova Z [Veratrum alkaloids. I] Veratrove alkaloidy I. In: Ceska Slov Farm (1994 Jul) 43(4):147-54 ISSN: 1210-7816 (Published in Slovak) Alkaloids represent an important group of therapeutically significant secondary metabolites. The plants of the genus Veratrum contain alkaloids with an antihypertensive effect. Also the genera Schoenocaulon and Zygadenus are sources of veratrum alkaloids. The present paper presents a survey of isolated alkaloids from the underground and aerial parts of 17 species of the genus Veratrum. The alkaloids occur as glycosides, aglycones or in the form of esters with various acids. In conformity with the IUPAC regulations for the nomenclature of steroids, Veratrum alkaloids were divided into 7 groups. The present paper lists the compounds of the first two groups, i.e. (1) alkaloids of the jervanine and veratranine types (I- XXIII), and (2) alkaloids with the cevanine skeleton (XXIV-XXXV). The individual compounds are characterized by their physico-chemical constants (melting point, optical rotation). €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CHUNG-KUO CHUNG HSI I CHIEH HO TSA CHIH***** Gao XS [Absorptive capacity of upper gastrointestinal tract with Chinese herbal medicine] In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1993 Jul) 13(7):433-5, 390 ISSN: 1003-5370 (Published in Chinese) 285 reports on the intoxication of Chinese herbal medicine per os were reviewed. The toxic symptoms occurred after oral administration for less than 10 min in about 110 reports. Some components of these herbal medicines might be absorbed and then reach effective level more rapidly. By segmental ligation of GI tract, experiments in rabbits, cats, rats or mice were conducted, in which principal ingredients of Rheum palmatum, Coptis chinensis, Veratrum nigrum, and aconitine were absorbed in esophagus or stomach within short period of time was observed. It suggested that the absorptive capacity of upper GI tract might have universal significance. The treatment of acute diseases by oral administration of Chinese herbal medicines is feasible. Registry Numbers: 302-27-2 (Aconitine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ **CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA* Lin N Gao X [Experimental observation on the absorption of Veratrum nigrum L. in the upper digestive tract] In: Chung Kuo Chung Yao Tsa Chih (1992 Jan) 17(1):43-5, inside back cover ISSN: 1001-5302 (Published in Chinese) This paper presents the experimental results of the absorption of orally administered Veratrum nigrum in the upper digestive tract. Taking the anomaly in ECG and intoxicative symptoms as the main parameters, we have found that Veratrum nigrum could be absorbed by the oral cavity, esophagus and stomach of mice or rats, and the esophagus absorbs better than the stomach. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY***** Fahim M Effect of veratrum alkaloids on right and left atrial receptors in the cat. In: Clin Exp Pharmacol Physiol (1979 May-Jun) 6(3):293-9 ISSN: 0305-1870 1. The effects of veriloid and veratridine on right and left atrial receptors have been studied in cats. 2. Threshold doses of these drugs for right atrial receptors were found to be almost twice those for left atrial receptors. Beyond threshold doses, however, the dose- response curves were similar. 3. The sensitivity of left atrial receptors to veratridine was not altered by an increase in PCO2 and/or decrease in PO2 of left atrial blood. Therefore, the difference in the behaviour of left and right atrial receptors to these drugs is not due to the differences in PO2 and PCO2 of blood in the two atria. They are more likely to be a feature of the regenerative regions of the receptors. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DEVELOPMENTAL BIOLOGY***** Campbell MA Brown KS Hassell JR Horigan EA Keeler RF Inhibition of limb chondrogenesis by a Veratrum alkaloid: temporal specificity in vivo and in vitro. In: Dev Biol (1985 Oct) 111(2):464-70 ISSN: 0012-1606 It has been demonstrated that jervine, a steroidal alkaloid derived from plants of the genus Veratrum, exerts teratogenic effects in several animal species. Defects were restricted to structures which depend upon normal chondrogenesis for their development. Here we report studies of the temporal specificity of cellular sensitivity using limb bud mesenchyme cells obtained from Day 10 mouse embryos. These cells, when grown as high-density "spot" cultures, undergo chondrogenesis in vitro. Prior to differentiation, exposure of limb cell cultures to jervine suppressed subsequent accumulation of cartilage proteoglycans. Treatment after differentiation had no significant effect. Additionally, there was a genetic component to jervine sensitivity: C57BL/6J mice were sensitive, whereas NIH Swiss- Webster mice were insensitive. This strain-dependent difference was observed both in vivo and in vitro, supporting the validity of limb mesenchyme spot cultures as a model for jervine-induced teratogenicity. Our studies indicate that jervine acts specifically during an early phase of the differentiation of mesenchyme into cartilage. It is likely that a specific stem cell population is the target tissue of this compound. Registry Numbers: 7005-18-7 (Methionine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****FOOD AND CHEMICAL TOXICOLOGY***** Crawford L Myhr B A preliminary assessment of the toxic and mutagenic potential of steroidal alkaloids in transgenic mice. In: Food Chem Toxicol (1995 Mar) 33(3):191-4 ISSN: 0278-6915 Impregnated CD2 transgenic mice, which contain multiple copies of a lambda gt10lacZ construct integrated into the genome of each cell, were given a predetermined estimated maximum tolerated dose of several steroidal alkaloids: Solanum glycoalkaloids from potato, alpha-chaconine and alpha-solanine; aglycones, solanidine and solasodine, and a Veratrum alkaloid, jervine. Observations were made of dams and foetuses for indications of toxicity and/or terata; some dam livers and foetuses were assayed for mutagenicity using the lacZ gene. Other dams were gavaged with a single dose of 75 mg all-trans- retinol/kg to serve as a reference teratogen. Unexpectedly, this level of retinol was not clearly teratogenic. The results of both positive and non-positive selection systems showed that the mutation frequencies in the livers of the dams dosed with alpha-chaconine, alpha-solanine and solanidine were three to four times higher than historically normal in the livers of this transgenic mouse strain. Registry Numbers: 126-17-0 (solasodine) 20562-02-1 (Solanine) 20562-03-2 (alpha-chaconine) 302-79-4 (Tretinoin) 469-59-0 (jervine) 80-78-4 (solanidine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****GENERAL PHARMACOLOGY***** Nanasi PP Kiss T Danko M Lathrop DA Different actions of aconitine and veratrum alkaloids on frog skeletal muscle. In: Gen Pharmacol (1990) 21(6):863-8 ISSN: 0306-3623 1. The electrophysiological effects of veratridine, cevadine and aconitine (10(-8)-2 x 10(-4), 2 x 10(-7)-2 x 10(-6) and 2 x 10(-6)- 10(-4) mol/l, respectively) were compared on frog muscle membrane using conventional microelectrodes. 2. Veratridine and aconitine were equally effective in depolarizing the resting membrane with the threshold concentration of 5 x 10(-5) mol/l. 3. Volleys of repetitive discharges and slow transient depolarizations were observed when single electrical stimuli were applied in the presence of veratridine (5 x 10(-8)-2 x 10(-5) mol/l), but not aconitine. Volleys with aconitine could be evoked only by repetitive stimulation; however no tendency of repolarization was observed following these volleys. Two orders of magnitude more aconitine than veratridine was required to induce volleys with similar parameters. 4. The effects of cevadine were similar to those of the corresponding concentrations of veratridine. 5. The observed differences between the electrophysiological actions of aconitine and veratrum alkaloids may be explained in part with differences in Na+ channel inactivation produced by these toxins, in addition to differences in their use- dependent behavior. Registry Numbers: 302-27-2 (Aconitine) 62-59-9 (Veratrine) 71-62-5 (Veratridine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Nanasi PP Varro A Bryant SH Lathrop DA Effects of veratrine on ion currents in single rabbit cardiomyocytes. In: Gen Pharmacol (1994 Dec) 25(8):1667-72 ISSN: 0306-3623 1. Voltage-clamp experiments were performed to determine the effects of veratrine (1 microgram/ml) on Na and K currents in isolated rabbit ventricular cardiomyocytes. 2. Veratrine did not affect the inward rectifier K current, increased the inactivation time constant of the transient outward current (I(to)) and induced a slowly decaying inward current component (Iv), which was sensitive to tetrodotoxin. 3. Inactivation of fast Na channels by application of short depolarizing prepulses to potentials between -90 and -50 mV prevented the development of Iv.Iv decayed biexponentially with time constants equal to 139 +/- 9.0 ms and 776 +/- 47 ms. The net amplitude of Iv and the time constants for its rapidly and slowly inactivating components were little affected by trains of conditioning prepulses to 0 mV. The contributions, however, of the fast and slow components to the net current were significantly altered by repetitive depolarizations. 4. These components of Iv are likely due to modification of open cardiac Na channels by veratrum alkaloids. Registry Numbers: 62-59-9 (Veratrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****HUMAN AND EXPERIMENTAL TOXICOLOGY***** Quatrehomme G Bertrand F Chauvet C Ollier A Intoxication from Veratrum album. In: Hum Exp Toxicol (1993 Mar) 12(2):111-5 ISSN: 0960-3271 Two new cases of Veratrum poisoning are described. Clinical symptoms occurred quickly, within 30 min. Vomiting, a fall in blood pressure and bradycardia were observed. The outcome was favourable in both cases, producing a cure without sequellae. Examination of the literature showed that such cases are nearly always accidental, resulting from the difficulty in distinguishing Veratrum album and Gentiana. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****HUMAN TOXICOLOGY***** Carlier P Efthymiou ML Garnier R Hoffelt J Fournier E Poisoning with Veratrum-containing sneezing powders. In: Hum Toxicol (1983 Apr) 2(2):321-5 ISSN: 0144-5952 1 Nine cases of accidental poisoning of children with sneezing powder are reported. Symptoms, besides sneezing, included gastrointestinal disturbances and syncope, whilst examination demonstrated bradycardia and hypotension. 2 The powder, as supplied, carried no information on its constituents but Veratrum alkaloids were identified on analysis. The signs and symptoms observed were compatible with poisoning from these compounds. 3 As a result of these observations, it was possible to trace the manufacturers and a change was made to a safer formulation. This example emphasises the value of toxic vigilance by Poison Control Centres. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF ANIMAL SCIENCE***** Keeler RF Teratogens in plants. In: J Anim Sci (1984 Apr) 58(4):1029-39 ISSN: 0021-8812 Many compounds synthesized by plants are known to be teratogenic in laboratory animals, but only a few have been shown by feeding trials to produce terata in livestock. Studies of plant teratogens affecting livestock have not moved forward in a systematic nor rapid way because of the logistical problems connected with such experiments in large animals. Information that has accumulated can be conveniently separated into three categories: (1) known teratogens in known teratogenic plants, (2) known teratogenic plants with unidentified teratogens, and (3) suspected teratogenic plants. Included in the first group are the teratogens from Lupinus, Veratrum, Conium and Leucaena genera; in the second group are included the Astragalus , Nicotiana and Trachymene genera; and in the third group are included Datura, Prunus , Sorghum and Senecio genera. Total available information in each case varies, but in a few instances considerable fundamental as well as practical information is now known. Research has provided enough information in a few instances to enable elimination of the practical problem or significant reduction in incidence. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF AUTONOMIC PHARMACOLOGY***** Giles TD Sander GE Comparative cardiovascular responses to intravenous capsaicin, phenyldiguanide, veratrum alkaloids and enkephalins in the conscious dog. In: J Auton Pharmacol (1986 Mar) 6(1):1-7 ISSN: 0144-1795 Cardiovascular responses to intravenous bolus doses of certain exogenous substances (capsaicin, phenyldiguanide, cryptenamine, veratrine sulphate) which act on chemoreceptors in the pulmonary or proximal arterial circulation were compared to the naturally occurring chemoreceptor agonist, leucineenkephalin (Leu5-ENK) in the conscious dog. Capsaicin (40 micrograms/kg) and phenyldiguanide (40 micrograms/kg) produced hypotension and bradycardia 5 to 12 sec after injection (P less than 0.05) followed by hypertension (P less than 0.05). Cryptenamine (5 micrograms/kg) produced only hypotension and bradycardia (P less than 0.05) whereas Leu5-ENK (35 micrograms/kg) produced only hypertension and tachycardia (P less than 0.05). The hypotension and bradycardia produced by capsaicin and phenyldiguanide occurred earlier than the pressor response to Leu5-ENK, capsaicin, and phenyldiguanide and the depressor response to veratrine (P less than 0.05). Cryptenamine (5 micrograms/kg) and Leu5-ENK (35 micrograms/kg) when given together had additive effects on heart rate but interacted significantly in influencing blood pressure (P less than 0.05). It is concluded that the early response to capsaicin and phenyldiguanide are compatible with stimulation of known pulmonary chemoreceptors (including J receptors) whereas the pressor effect of phenyldiguanide and Leu5-ENK and the depressor response to veratrum alkaloids are due to activation of receptors in the proximal arterial circulation. The influence of Leu5-ENK on the haemodynamic response to veratrine suggest that ENK may modulate the Bezold-Jarisch reflex. Registry Numbers: 102-02-3 (phenyl biguanide) 404-86-4 (Capsaicin) 58822-25-6 (Enkephalin, Leucine) 62-59-9 (Veratrine) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JOURNAL OF GENERAL PHYSIOLOGY***** Leibowitz MD Schwarz JR Holan G Hille B Electrophysiological comparison of insecticide and alkaloid agonists of Na channels. In: J Gen Physiol (1987 Jul) 90(1):75-93 ISSN: 0022-1295 Macroscopic currents in Na channels were recorded from adult frog skeletal muscle under voltage clamp as various toxins were added to the bathing medium. Veratridine, cevadine, and 3-(4-ethoxybenzoyl)- veracevine modified the Na channels in a use-dependent manner during depolarizations and held them open for 3, 2.4, and 1.2 s, respectively, at -90 mV. The three alkaloids modified channels in the same way. Activation gating was shifted about -100 mV by the modification, and reversible closing of the channels by strong hyperpolarizations slowed reversal of the modification. The synthetic insecticides deltamethrin, EDO, GH739, and GH414 also modified channels during depolarizations that opened channels. The modification lasted 3 s with deltamethrin, but only 3-5 ms with the others. Hyperpolarization speeded the shutting off of current in insecticide-modified channels, but no reversible activation gating could be demonstrated. The ionic selectivity, PNa/PNH4, of channels was decreased by all of the toxins. This ratio was 0.11 in normal channels, 0.26 in insecticide-modified channels, and 0.7-1.6 in veratrum-alkaloid-modified channels. During use-dependent modification, the veratrum alkaloids reduced the total Na current markedly, while deltamethrin did not. Thus, alkaloid and insecticide modifications share many features but differ in how much the conducting properties of the pore are changed and whether the channel can close reversibly while the toxin remains bound. Registry Numbers: 7440-23-5 (Sodium) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****NEOPLASMA***** Fuska J Fuskova A Vassova A Voticky Z New substances with cytotoxic and antitumor effects. IV. In vitro effect of some veratrum alkaloids and their derivatives on leukemia P388 cells. In: Neoplasma (1981) 28(6):709-14 ISSN: 0028-2685 Some Veratrum alkaloids and their derivatives exhibited an in vitro cytotoxic effect on leukemia P388 cells, depending on the structure of the skeleton of the molecule, particularly on the type of the heterocycle attached to C-20. Veracintine and 20-(2-methyl-1-pyrrolin- 5-yl)-4-pregnen-3-one, which proved to be the most effective, inhibited incorporation of uridine, and to a lesser extent that of L- valine into P388 cells fractions. After a brief reaction (15 min), these substances became irreversibly bound in the P388 cells and stopped their further in vitro proliferation. The cytotoxic effect of veracintine became enhanced by sublethal doses of tubercidine (phase of maximum lethality of G1). Registry Numbers: 69-33-0 (Tubercidin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Fuska J Fuskova A Vassova A Voticky Z NEW SUBSTANCES WITH CYTOTOXIC AND ANTITUMOR EFFECTS. IV. IN VITRO EFFECT OF SOME VERATRUM ALKALOIDS AND THEIR DERIVATIVES ON LEUKEMIA P388 CELLS In: Neoplasma (1981) 28(6):709-714 ISSN: 0028-2685 Some Veratrum alkaloids and their derivatives exhibited an in vitro cytotoxic effect on leukemia P388 cells, depending on the structure of the skeleton of the molecule, particularly on the type of the heterocycle attached to C-20. Veracintine and 20-(2-methyl-1-pyrrolin- 5-yl)-4-pregnen-3-one, which proved to be the most effective, inhibited incorporation of uridine, and to a lesser extent that of L- valine into P388 cells fractions. After a brief reaction (15 min), these substances became irreversibly bound in the P388 cells and stopped their further in vitro proliferation. The cytotoxic effect of veracintine became enhanced by sublethal doses of tubercidine (phase of max lethality at G1). (Author abstract) (12 Refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****VUTRESHNI BOLESTI***** Marinov A Koev P Mirchev N [Electrocardiographic studies of patients with acute hellebore (Veratrum album) poisoning] Elektrokardiografski prouchvaniia pri bolni s ostro otraviane s chemerika (Veratrum album). In: Vutr Boles (1987) 26(6):36-9 ISSN: 0506-2772 (Published in Bulgarian) In 12 patients, 20 to 80 years of age, 6 men and 6 women, with acute hellebore (Veratrum album) intoxication the electrocardiographic changes were studied. In 10 of them a characteristic ECG pattern was found: sinus bradycardia 38-40/m, shortening of the interval PQ up to 0.12-0.08 s and QTc up to 0.36-0.32 s, slow intraventricular conduction--transitory right and incomplete left bundle-branch block, rhythm disorders--atrial and substitutional ventricular extrasystoles, nodal rhythm (I patient), disturbed ventricular repolarization--depression of ST-segment, low and (or) pointed T waves. The authors are of the opinion that the bradycardia is due to a reflexively increased vagal tonus but the other changes of the ECG are caused by the direct toxic action of the hellebore alkaloids on the myocardium. This suggestion is supported by the fact that atropine corrects the bradycardia but not the other pathological changes of the ECG. They are beneficially influenced by the fast elimination of the toxins and the application of cardiotropic means-- atriphos, cocarboxylase, vitamins of the group B. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****WIENER KLINISCHE WOCHENSCHRIFT***** Hruby K Lenz K Krausler J [Veratrum album poisoning (author's transl)] Vergiftung mit Veratrum album (weisser Germer). In: Wien Klin Wochenschr (1981 Sep 4) 93(16):517-9 ISSN: 0043-5325 (Published in German) Ingestion of plant material rarely gives rise to manifest clinical intoxication. This is due to the relatively low toxicity of most of the poisonous plants of Central Europe. Veratrum album is an important exception on account of its highly toxic alkaloids. Seven cases of overt intoxication from veratrum album have been reported to the Austrian Poison Information Centre during the past 5 years. On the basis of these case reports toxicological and clinical aspects of this rare form of poisoning are discussed. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€