piperidines and coniine

Rhabdomyolysis (R) is a complex condition involving the rapid dissolution of damaged or injured skeletal muscle. This leads to the direct release of intracellular components, including myoglobin, creatine kinase, aldolase, and lactate dehydrogenase, as well as electrolytes, into the bloodstream and extracellular space. Clinically, R shows a triad of symptoms: myalgia, limb weakness, and myoglobinuria without hematuria, while myoglobin has been recognized as playing a part in the development of acute kidney injury. Coturnism is a relatively rare disease, mostly found in the European countries bordering the Mediterranean Sea, characterized by acute R. It follows the consumption of Coturnix coturnix, a species of quails common in Europe, that have ingested the toxic substances (and especially coniine) present in the herbaceous plant called hemlock (Conium maculatum). Coniine may be lethal at a dose of 150 mg but it has neurotoxic effects at smaller doses, with acute R and acute kidney injury. Freezing and cooking the meat does not inactivate the alkaloids present in the birds' flesh and digestive tract. The clinical course of coturnism includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, R and acute kidney injury. In appropriate geographical and temporal settings, it should be considered when diagnosing patients with acute R. The genetic, biochemical and epidemiological characteristics of coturnism are not yet fully known, while we wait reliable data from experimental studies.

Topics: Acute Kidney Injury; Alkaloids; Animals; Foodborne Diseases; Humans; Muscle, Skeletal; Piperidines; Plant Poisoning; Quail; Rhabdomyolysis

The aim of this paper is to highlight the symptomatology in three Conium maculatum intoxication incidents, one of which was fatal. A number of studies were reviewed in order to update and summarize the relevant literature on the incidence, sociodemographic variables, method of poisoning, pathophysiology, diagnosis, variables associated with survival and fatality, management, and treatment of C. maculatum intoxication as well as the biosynthesis and biological effects of poison hemlock alkaloids. Results show that hemlock poisoning is relatively rare, although incidence varies in different regions, despite its worldwide distribution. Hemlock poisoning is more common in European and especially Mediterranean countries. The majority of the patients are adult males over 38 years of age. The clinical course of hemlock poisoning includes neurotoxicosis, tremor, vomiting, muscle paralysis, respiratory paralysis/failure, rhabdomyolysis, and acute renal failure. The therapeutic management focuses on absorption reduction, close observation for complications, and supportive therapy (especially for respiration). Acute occurrence is severe and life-threatening, but the survival rate is high if treatment is provided promptly. Recovery is rapid, generally taking only a few days.

Topics: Accidents; Aged; Alkaloids; Animals; Antidotes; Antiemetics; Charcoal; Chromatography, Liquid; Conium; Gas Chromatography-Mass Spectrometry; Gastric Lavage; Humans; Livestock; Male; Molecular Structure; Phytotherapy; Piperidines; Plant Poisoning; Respiratory Paralysis; Rhabdomyolysis; Suicide

Coniine, a polyketide-derived alkaloid, is poisonous to humans and animals. It is a nicotinic acetylcholine receptor antagonist, which leads to inhibition of the nervous system, eventually causing death by suffocation in mammals. Coniine's most famous victim is Socrates who was sentenced to death by poison chalice containing poison hemlock in 399 BC. In chemistry, coniine holds two historical records: It is the first alkaloid the chemical structure of which was established (in 1881), and that was chemically synthesized (in 1886). In plants, coniine and twelve closely related alkaloids are known from poison hemlock (

Topics: Alkaloids; Animals; Biosynthetic Pathways; Humans; Piperidines; Plants; Structure-Activity Relationship

A catalytic conjunctive cross-coupling reaction is developed that allows the construction of chiral organoboronic esters from alkylboron ate complexes and alkyl iodide electrophiles. The process occurs most efficiently with a Ni/Pybox-comprised catalyst and with an acenapthoquinone-derived boron ligand. Because of the broad functional group tolerance of this reaction, it can be a versatile tool for organic synthesis. Applications to the construction of (

Topics: Alkaloids; Boronic Acids; Catalysis; Esters; Indolizines; Molecular Structure; Nickel; Piperidines

Sarraceniaceae is a New World carnivorous plant family comprising three genera: Darlingtonia, Heliamphora, and Sarracenia. The plants occur in nutrient-poor environments and have developed insectivorous capability in order to supplement their nutrient uptake. Sarracenia flava contains the alkaloid coniine, otherwise only found in Conium maculatum, in which its biosynthesis has been studied, and several Aloe species. Its ecological role and biosynthetic origin in S. flava is speculative. The aim of the current research was to investigate the occurrence of coniine in Sarracenia and Darlingtonia and to identify common constituents of both genera, unique compounds for individual variants and floral scent chemicals. In this comprehensive metabolic profiling study, we looked for compound patterns that are associated with the taxonomy of Sarracenia species. In total, 57 different Sarracenia and D. californica accessions were used for metabolite content screening by gas chromatography-mass spectrometry. The resulting high-dimensional data were studied using a data mining approach. The two genera are characterized by a large number of metabolites and huge chemical diversity between different species. By applying feature selection for clustering and by integrating new biochemical data with existing phylogenetic data, we were able to demonstrate that the chemical composition of the species can be explained by their known classification. Although transcriptome analysis did not reveal a candidate gene for coniine biosynthesis, the use of a sensitive selected ion monitoring method enabled the detection of coniine in eight Sarracenia species, showing that it is more widespread in this genus than previously believed.

Topics: Alkaloids; Data Mining; Gas Chromatography-Mass Spectrometry; Genes, Plant; Metabolomics; Phylogeny; Piperidines; Plant Proteins; Polyketide Synthases; Sarraceniaceae; Species Specificity; Transcriptome

Toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), is manifested by characteristic nicotinic clinical signs including excitement, depression, hypermetria, seizures, opisthotonos via postsynaptic nicotinic receptors. There is limited knowledge about the role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine in the literature. The present study was undertaken to evaluate the possible role of presynaptic nicotinic receptors on the pharmacological and toxicological effects of coniine. For this purpose, the rat anococcygeus muscle and guinea-pig atria were used in vitro. Nicotine (100 μM) elicited a biphasic response composed of a relaxation followed by contraction through the activation of nitrergic and noradrenergic nerve terminals in the phenylephrine-contracted rat anococcygeus muscle. Coniine inhibited both the nitrergic and noradrenergic response in the muscle (-logIC(50) = 3.79 ± 0.11 and -logIC(50) = 4.57 ± 0.12 M, respectively). The effect of coniine on nicotinic receptor-mediated noradrenergic transmission was also evaluated in the guinea-pig atrium (-logIC(50) = 4.47 ± 0.12 M) and did not differ from the -logIC(50) value obtained in the rat anococcygeus muscle. This study demonstrated that coniine exerts inhibitory effects on nicotinic receptor-mediated nitrergic and noradrenergic transmitter response.

Topics: Alkaloids; Animals; Dose-Response Relationship, Drug; Guinea Pigs; Heart Atria; Male; Muscle, Skeletal; Myocardium; Piperidines; Rats; Receptors, Nicotinic; Synapses; Synaptic Transmission

Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetyl-CoA and three malonyl-CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full-length enzymes by feeding different starter-CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl-CoA as a starter-CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl-CoA and two malonyl-CoAs.

Topics: Acyltransferases; Alkaloids; Amino Acid Sequence; Cloning, Molecular; Conium; Genes, Plant; Kinetics; Metabolic Networks and Pathways; Models, Biological; Molecular Sequence Data; Phylogeny; Piperidines; Plant Proteins; Plants, Toxic; Polyketide Synthases; Sequence Homology, Amino Acid; Substrate Specificity

Coniine is an optically active toxic piperidine alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of coniine actions at fetal muscle-type nAChR is lacking. The present study compared (-)-coniine, (+)-coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, α-conotoxins (CTx) EI and GI were used to antagonize the actions of (+)- and (-)-coniine in TE-671 cells. (-)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (+)-coniine, suggesting stereoselectivity by the receptor. The pyridine alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both coniine enantiomers demonstrating concentration-dependent coagonism and selective antagonism. These results provide pharmacological evidence that the piperidine alkaloid coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner.

Topics: Acetylcholine; Alkaloids; Animals; Calcium Channel Blockers; Cell Line; Cell Line, Tumor; Conotoxins; Crystallization; Dose-Response Relationship, Drug; Female; Fetal Movement; Goats; Humans; Mandelic Acids; Muscle, Skeletal; Piperidines; Pregnancy; Receptors, Nicotinic; Stereoisomerism

Access to nonracemic amino ketones via a hydrozirconation/transmetalation/acylation sequence applied to Boc-protected 1-aminobut-3-enes is presented. This method was applied to the stereoselective synthesis of cyclic imines (or iminiums) which were diastereoselectively converted into 2-cis-substituted and 2,6-cis-disubstituted piperidines. The potential of this approach in the field of alkaloid synthesis was illustrated by the synthesis of (-)-coniine and (-)-indolizidine 209D. Furthermore, access to indolizidines bearing a quaternary center could also be envisioned through this strategy.

Topics: Acylation; Alkaloids; Indolizidines; Indolizines; Molecular Structure; Piperidines; Stereoisomerism

The catalytic dynamic resolution (CDR) of rac-2-lithio-N-Boc-piperidine using chiral ligand 8 or its diastereomer 9 in the presence of TMEDA has led to the highly enantioselective syntheses of both enantiomers of 2-substituted piperidines using a wide range of electrophiles. The CDR has been applied to the synthesis of (R)- and (S)-pipecolic acid derivatives, (+)-beta-conhydrine, (S)-(+)-pelletierine, and (S)-(-)-ropivacaine and the formal synthesis of (-)-lasubine II and (+)-cermizine C.

Topics: Alkaloids; Amides; Catalysis; Heterocyclic Compounds, 2-Ring; Lithium; Molecular Conformation; Organometallic Compounds; Pipecolic Acids; Piperidines; Quinolizines; Ropivacaine; Stereoisomerism; Thermodynamics

Topics: Alkaloids; Alkylation; Amides; Anisomycin; Combinatorial Chemistry Techniques; Ketones; Lactams; Molecular Structure; Oxidation-Reduction; Piperidines; Pyrrolidines; Stereoisomerism

Hemlock was used as an analgesic in certain ethnopharmacological traditions and there has been no record about the antinociceptive effect of coniine which is the major alkaloid compound of Hemlock.. The present study was undertaken to evaluate the possible antinociceptive activity of coniine.. Antinociceptive activity of coniine was tested dose in Hotplate test (thermal pain model) and in Writhing test (chemical pain model) in different nociception models.. Coniine caused a prolongation in reaction time in Hotplate test at 20mg/kg dose. In addition, it was observed that coniine decreased the number of writhes in Writhing test. Both data indicated an antinociceptive effect of coniine. A rotarod test was also conducted in order to clarify, whether this activity was related with a loss of locomotion or with an analgesic activity. None of the chemical agents at those doses used in experiments caused a loss of locomotor activity. It was also shown that antinociceptive effect of morphine was potentialized by coniine which was inhibited by nicotinic receptor blocker mecamylamine (1mg/kg).. Coniine has antinociceptive effect via the nicotinic receptors. A pharmacological assessment about the painless death of Socrates due to Hemlock (coniine) toxicity has also been presented by using this data.

Topics: Acetic Acid; Alkaloids; Analgesics; Animals; Conium; Drug Synergism; Male; Mecamylamine; Mice; Morphine; Nicotinic Antagonists; Pain; Piperidines; Plant Extracts

We describe a tandem Mitsunobu/3,3-sigmatropic rearrangement of allylic azides on a chiral auxiliary system that favors one regioisomer thanks to its exceptional steric bias. The sequence may be completed by the oxidative cleavage of the auxiliary or by a ring-closing metathesis reaction that produces a carbo- or heterocycle directly and a recyclable form of the chiral auxiliary. Applications of the methodology to the total synthesis of (+)-coniine, (+)-lentiginosin, and (+)-pumiliotoxin C are reported.

Topics: Alkaloids; Allyl Compounds; Amino Acids; Animals; Azides; Heterocyclic Compounds; Piperidines; Quinolines; Stereoisomerism

Coniine, one of the major toxic alkaloids present in poison hemlock ( Conium maculatum), occurs in two optically active forms. A comparison of the relative potencies of (+)- and (-)-coniine enantiomers has not been previously reported. In this study, we separated the enantiomers of coniine and determined the biological activity of each enantiomer in vitro and in vivo. The relative potencies of these enantiomers on TE-671 cells expressing human fetal nicotinic neuromuscular receptors had the rank order of (-)-coniine > (+/-)-coniine > (+)-coniine. A mouse bioassay was used to determine the relative lethalities of (-)-, (+/-)-, and (+)-coniine in vivo. The LD 50 values of the coniine enantiomers were 7.0, 7.7, and 12.1 mg/kg for the (-)-, (+/-)-, and (+)- forms of coniine, respectively. The results from this study demonstrate that there is a stereoselective difference in the in vitro potencies of the enantiomers of coniine that directly correlates with the relative toxicities of the enantiomers in vivo.

Topics: Alkaloids; Animals; Cell Line, Tumor; Humans; Lethal Dose 50; Mice; Molecular Structure; Piperidines; Stereoisomerism

Conjugate addition of lithium (S)-N-benzyl-N-alpha-methylbenzylamide to a range of alpha, beta-unsaturated Weinreb amides proceeds with high levels of diastereoselectivity (>95% de). The beta-amino Weinreb amide products may be transformed into beta-amino ketones via reactions with Grignard reagents, while treatment with DIBAL-H furnishes beta-amino aldehydes. Trapping of the aldehyde via Wadsworth-Emmons reaction and subsequent manipulation offers an efficient route to homochiral delta-amino acid derivatives and 2-substituted piperidines. The application of this methodology for the synthesis of (S)-coniine is demonstrated.

Topics: Aldehydes; Alkaloids; Amides; Ketones; Lithium Compounds; Molecular Structure; Piperidines

A procedure was developed for the determination of nickel(II) in water samples by inductively coupled plasma atomic emission spectrometry (ICP-AES) after preconcentration on coniine dithiocarbamate (CDC) supported by Borassus Flabellifer inflorescence. The sorbed element was subsequently eluted with 0.4M nitric acid and the acid eluates are analysed by ICP-AES. The influence of various parameters such as pH, flow rate of sample, eluent concentration, volume of the sample and volume eluent were investigated. Under the optimal conditions, nickel in aqueous sample was concentrated about 100-fold. Nickel recovery was obtained by the proposed method in range of 98.9-99.9%. This method is also applied for the analysis of spiked and natural water samples. The results provide strong evidence to support the hypothesis of an adsorption mechanism.

Topics: Alkaloids; Chromatography; Hydrogen-Ion Concentration; Nickel; Nitric Acid; Piperidines; Spectrophotometry, Atomic; Water Pollutants, Chemical; Water Pollution

(S)-Coniine is made using a reaction which assembles the piperidine ring by the sequential formation of four new chemical bonds and installs the C-2 stereogenic centre with high levels of diastereocontrol (90% de).

Topics: Alkaloids; Aziridines; Molecular Structure; Piperidines; Plants; Stereoisomerism

[reaction: see text] Sequences of lithiation-substitution, enantioselective hydrogenation, and diastereoselective lithiation-substitution provide efficient highly enantioselective syntheses of 2-substituted and cis and trans 2,6-disubstituted piperidines. The methodology is demonstrated by syntheses of (-)-coniine, (-)-solenopsin A, and (-)-dihydropinidine as their hydrochlorides.

Topics: Alkaloids; Analgesics; Piperidines; Stereoisomerism

Phytochemical investigations of Aloe sabaea afforded a new chlorinated amide, N-4'-chlorobutylbutyramide, and the toxic piperidine alkaloids coniine, gamma-coniceine and the quarternary N,N-dimethylconiine. This is the first report of the occurrence of a chlorinated compound in the Aloeaceae family.

Topics: Alkaloids; Aloe; Piperidines; Plants, Medicinal; Pyridines

Topics: Alkaloids; Animals; Female; Foodborne Diseases; Humans; Middle Aged; Piperidines; Quail; Rhabdomyolysis

Coniine, an alkaloid from Conium maculatum (poison hemlock), is a known teratogen in many domestic species with maternal ingestion resulting in arthrogryposis of the offspring. We have previously shown that rats are not susceptible and rabbits only weakly susceptible to coniine-induced arthrogryposis. However, the chick embryo does provide a reproducible laboratory animal model of coniine-induced teratogenesis. The reason for this cross-species variation is unknown. The purpose of this study was to evaluate coniine binding to nicotinic receptors and to measure coniine metabolism in vitro between susceptible and non-susceptible species. Using the chick model, neither the peripheral nicotinic receptor antagonist d-tubocurarine chloride nor the central nicotinic receptor antagonist trimethaphan camsylate blocked the teratogenesis or lethality of 1.5% coniine (50 microliters/egg). Trimethaphan camsylate enhanced coniine-induced lethality in a dose-dependent manner. Neither nicotinic receptor blocker prevented nicotine sulfate-induced malformations but d-tubocurarine chloride did block lethality in a dose-dependent manner. Competition by coniine for [125I]-alpha-bungarotoxin to nicotinic receptors isolated from adult rat diaphragm and chick thigh muscle and competition by coniine for [3H]-cytisine to receptors from rat and chick brain were used to assess coniine binding to nicotinic receptors. The IC50 for coniine in rat diaphragm was 314 microM while that for chick leg muscle was 70 microM. For neuronal nicotinic receptors, the IC50s of coniine for maternal rat brain, fetal rat brain, and chick brain were 1100 microM, 820 microM, and 270 microM, respectively. There were no differences in coniine biotransformation in vitro by microsomes from rat or chick livers. Differences in apparent affinity of coniine for nicotinic receptors or differences in the quantity of the nicotinic receptor between the rat and chick may explain, in part, the differences in susceptibility of coniine-induced teratogenesis between these two species.

Topics: Abnormalities, Drug-Induced; Alkaloids; Analgesics; Animals; Biotransformation; Brain; Chick Embryo; Embryo, Nonmammalian; Male; Microsomes, Liver; Muscle, Skeletal; Nicotinic Antagonists; Piperidines; Rats; Rats, Sprague-Dawley; Survival Rate

Topics: Alkaloids; Child, Preschool; Hemlock; Humans; Male; Piperidines; Plant Poisoning; Plants, Toxic; Pyridines

Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.

Topics: Alkaloids; Animals; Arthrogryposis; Cerebral Hemorrhage; Chick Embryo; Nicotine; Piperidines; Teratogens

Conium maculatum (poison hemlock, CM) is teratogenic in several domestic species, presumably due to its piperidine alkaloids, including coniine, which has been verified to be teratogenic in cattle. Coniine/CM teratogenicity culminates in production of arthrogryposis. The purpose of this study was to evaluate coniine-induced teratogenicity in two laboratory animal species, Sprague-Dawley rats and New Zealand white rabbits. Pregnant rats were given coniine (25 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 16-18. Pregnant rabbits were given coniine (40 mg/kg body weight) by oral gavage at 8-hour intervals on gestation days 20-24. Rats were killed on day 19 and rabbits on day 29. Fetuses were immediately removed, weighed, and examined for external abnormalities. Alternate fetuses were either stained for skeletal examinations with alizarin red-S or fixed in Bouin's solution for visceral examination. Symptoms of maternal intoxication due to coniine administration were observed in both the rat and the rabbit, and higher doses were uniformly lethal. Rabbits treated with coniine appeared to lose more weight and eat less than controls, but there was no statistically significant difference between groups. Fetal weights were significantly lower in coniine-exposed rat and rabbit fetuses indicating fetotoxicity. The only statistically significant treatment-related visceral or skeletal malformation was a reduction of cranial ossification of rabbit fetuses, probably related to maternal toxicity. Coniine-exposed rabbit litters tended to be affected by arthrogryposis (no bony deformities noted on skeletal exam) more than controls (2/6 vs. 0/9).

Topics: Abnormalities, Drug-Induced; Alkaloids; Animals; Arthrogryposis; Birth Weight; Feeding Behavior; Female; Fetal Death; Litter Size; Piperidines; Pregnancy; Rabbits; Rats; Rats, Sprague-Dawley; Teratogens

We report the clinical and histological findings in patients with acute renal failure caused by the ingestion of wildfowl who had eaten hemlock buds. Neurotoxic effects were accompanied by rhabdomyolysis, myoglobinuria, and acute tubular necrosis. Histological studies showed diffuse degeneration of the tubular epithelium. Immunohistological studies demonstrated the presence of myoglobin and actin in renal tubular cells.

Topics: Acute Kidney Injury; Alkaloids; Animals; Birds; Humans; Kidney; Kidney Tubular Necrosis, Acute; Piperidines; Plant Poisoning

Cattle in two herds developed signs of bloating, increased salivation and lacrimation, depression, respiratory distress, ataxia, and death after ingestion of hay that contained large amounts of poison hemlock (Conium maculatum). Twenty of 30 Angus cows and calves were affected in the first herd (2 died). In the second herd, 5 of 30 Holstein heifers were affected (1 died). The Conium alkaloids, coniine and gamma-coniceine, were quantified in the hay, the plants from the responsible hayfield, and the urine of affected animals.

Topics: Alkaloids; Animal Feed; Animals; Cattle; Cattle Diseases; Chromatography, Gas; Female; Gastrointestinal Contents; Mass Spectrometry; Medicago sativa; Piperidines; Plant Poisoning; Plants, Toxic; Rumen

In the past, hemlock poisoning was only known for its neurotoxic effects; quite recently non-neurological features, consisting of rhabdomyolysis and acute renal failure, have been also described. Here we report our experience with these clinical findings, which we frequently observe in accidental hemlock poisoning. Between 1972 and 1990 we studied 18 patients: 17 of them were poisoned by conline (an alkaloid of Conium maculatim) in Apulia (Italy), and one by cicutoxin (the active principle of water hemlock) in New Mexico (USA). In the non-rapidly-fatal cases we tested myoglobinuria, serum muscle enzymes, and renal function. In the patients with acute renal failure we performed microscopical examination of kidney specimens; immunohistochemistry was carried out to identify myoglobin and actin in tubules. Coniine was detected in urine, serum, or tissues. Neurological features were present in all of our cases: coniine had a curare-like effect on the neuromuscular junction, whereas cicutoxin was convulsant on the central nervous system. In addition rhabdomyolysis was noted in the 17 subjects poisoned by coniine. Acute renal failure was observed in five patients; it was confirmed by histological evidence of tubular necrosis with intratubular deposition of myoglobin and actin released by rhabdomyolysis. Our cases seem to be the first with histopathologically proven acute tubular necrosis in coniine intoxication. In conclusion, in hemlock poisoning neurotoxic manifestations may be accompanied by rhabdomyolysis and acute tubular necrosis; increased awareness of these clinical features is recommended in order to improve the diagnostic and therapeutic procedure.

Topics: Adult; Aged; Alkaloids; Alkynes; Diynes; Fatty Alcohols; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Nervous System Diseases; Piperidines; Plant Poisoning; Rhabdomyolysis

Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.

Topics: Abnormalities, Multiple; Alkaloids; Anabasine; Animals; Bone and Bones; Cleft Palate; Female; Goat Diseases; Goats; Nicotiana; Piperidines; Plant Extracts; Plant Poisoning; Plants, Toxic; Pregnancy; Pyridines; Teratogens

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Alkaloids; Analgesics; Animals; Birds; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Middle Aged; Piperidines; Rhabdomyolysis; Seasons

Topics: Alkaloids; Animals; Female; Male; Piperidines; Plant Poisoning; Plants, Toxic; Rabbits

Topics: Alkaloids; Animals; Congenital Abnormalities; Female; Piperidines; Plant Poisoning; Pregnancy; Swine; Swine Diseases

Cleft palates were induced in newborn pigs of gilts fed Conium maculatum seed or plant during gestation days 30 through 45. Twelve of 23 newborn pigs born to 3 gilts given Utah-grown C maculatum seed and 9 of 12 newborn pigs born to a single gilt given the fresh Utah spring-growth C maculatum plant had cleft palates. The cleft palates ranged from a unilateral cleft, involving only 1 side of the palate, to a full bilateral cleft. Brachygnathia was also observed in some of these newborn pigs with cleft palate. Other malformations were not observed. Chemical analysis of seed and plant samples indicated that gamma-coniceine was the responsible teratogenic alkaloid. A daily dose of plant or seed that provided greater than or equal to 1.07 mg of gamma-coniceine/kg of body weight fed to gilts during the 30th through the 45th day of pregnancy resulted in teratogenic effects.

Topics: Alkaloids; Animals; Animals, Newborn; Chromatography, Gas; Cleft Palate; Female; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Pregnancy Complications; Pyridines; Seeds; Swine; Swine Diseases

Cows, ewes, and mares varied considerably in susceptibility to toxicoses from the oral administration of the piperidine alkaloid, coniine. Cows were most susceptible and ewes least. Only calves had teratogenic effects from maternal administration of coniine during gestation; lambs and foals were apparently resistant. Results suggest that the marked differences between cattle and sheep are probably not due to variation in gut absorption or rumen metabolism.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Alkaloids; Animals; Ataxia; Cattle; Cattle Diseases; Female; Horse Diseases; Horses; Piperidines; Plants, Toxic; Pregnancy; Sheep; Sheep Diseases

The plant Conium maculatum produced congenital defects in calves born to cows gavaged the fresh green plant during days 50-75 of gestation. Both arthrogryposis and spinal curvature were produced and were similar to the defects produced by the piperidine alkaloid coniine. The arthrogrypotic manifestations of the condition markedly increased in severity as the animals aged. Animals gavaged dry plant had either normal or equivocally deformed offspring. A number of chain length and ring saturation analogs of coniine were not teratogenic. No congenital defects arose in offspring from maternal inhalation of either the teratogenic alkaloid coniine, or from the teratogenic green plant.

Topics: Abnormalities, Drug-Induced; Alkaloids; Animals; Arthrogryposis; Cattle; Cattle Diseases; Female; Piperidines; Plants, Toxic; Pregnancy; Structure-Activity Relationship

Topics: Alkaloids; Animals; Birds; Cats; Cochlear Nerve; Cordotomy; Electric Stimulation; Electrocardiography; Electroencephalography; Gallamine Triethiodide; Paralysis; Pharmacology; Piperidines; Research; Seizures; Spinal Cord; Strychnine; Toxicology

Topics: Alkaloids; Cats; Ganglionic Blockers; Neuromuscular Junction; Pharmacology; Piperidines; Research; Spinal Nerves

Topics: Alkaloids; Hypertension; Hypertension, Renal; Piperidines; Research; Solanine; Spectrophotometry

Topics: Alkaloids; Humans; Lysine; Piperidines; Solanine

Topics: Alkaloids; Conium; Piperidines; Solanine

Topics: Alkaloids; Bacteria; Humans; Nicotine; Piperidines; Solanine; Strychnine