[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Me...[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Method] The security of arecoline hydrobromide was evaluated based on acute toxicity tests; the ranges of safe medication, tolerability and toxicity as well as ＂Three-induced＇ effects （carcinogensis, mutagene- sis and teratogenesis） and reproductive toxicity were summarized according to the combinations of experimental results, papers and clinical effects. E Result] The results of acute toxicity tests in mice and rats showed that LD^0 （50% lethal dosages） of arecoline hydrobromide in mice was 691.83 mg/（kg.BW） and 95% incredible range of its LDso was 642.92 -744.47 mg/（ kg. BW）, and LDso of arecoline hydrobromide in rats was 2 054 mg/（kg.BW） and 95% incredible range of its LDso was 1 908 -2 210 mg/（kg.BW）. Its LDso value was hundreds times higher than the recommen- ded clinical dosage [ 1 -5 mg/（kg-BW） ], therefore it is safe to apply in clinic. The research results of ranges of safe medication, tolerability and toxicity showed that arecoline hydrobromide could entirely dispel the dog Diphyllobothrium, Spirometra mansoni, Dipylidium mesocestoides, Linea- tus and Cysticercus at dosages of 2 -3 mg/（ kg.BW）, and the same effects to Railletina tapeworm of chickens and Drepanidotaenia lanceolata of duck and goose at dosages of I -2 mg/（kg.BW）. The arecoline hydrobromide had muscarinic effects as side-effects and could cause vomiting, di- arrhea and other clinical symptoms to discharge the paralyzed worm from livestock body rapidly and completely. The arecoline hydrobromide had ＂Three-induced＂ effects and reproductive toxicity when it was used as antitapeworm drug with long-term, sustained and a large number of drug us- age, rather than used in clinical application with shorter time and lower dosage of administration. [ Conclusion] The arecoline hydrobromide is low- toxic substance and has a certain of toxicity such as ＂Three-induced＂ effects and reproductive toxicity at high-dosages application, and there are good effects on livestock and poultry tapeworm at the clinical recommended dosacles without ＂Three-induced＂ effects and reproductive toxicity.展开更多
Taeniasis and cysticercosis in domestic animals belong to zoonosis and seriously threaten the public health security. Especially the cysticercosis and echinococcosis caused by the tapeworm eggs have great harms to bod...Taeniasis and cysticercosis in domestic animals belong to zoonosis and seriously threaten the public health security. Especially the cysticercosis and echinococcosis caused by the tapeworm eggs have great harms to bodies because they can attack many organs of body. According to the combination of experimental results and literature materials, the morphology and transmission mode of taenia and cysticercus, the prevalence status and monitoring of taeniasis and cysticercosis as well as the antitapeworm mechanism, comparative analysis to other drugs, expelling tapeworm tests in vitro, dose determining tests and usage notes of arecoline hydrobromide were expounded in detail. It provides a theoretical basis for prevention of taeniasis and cysticarcosis and more scientific usage of arecoline hydrobromide and thus relieves the harms of taeniasis and cysticercosis and ensuring the public health security.展开更多
Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of a...Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K^＋ current （/hERG）. Methods Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the /hI=RG before and after the exposure to arecoline. Results Arecoline decreased the amplitude and the density of the /bERG in a concentration-dependent manner （IC5o=9.55 μmol/L）. At test potential of ＋60 mV, the magnitude of lhERG tail at test pulse of -40 mV was reduced from （151.7±6.2） pA/pF to （84.4±7.6） pA/pF （P 〈0.01, n=20） and the magnitude of IhERG tail at test pulse of -110 mV was reduced from （-187.5±9.8） pA/pF to （-97.6±12.6） pA/pF （P 〈0.01, n=20）. The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of IhERG was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of IhERG by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. Conclusion Arecoline could potently block IhERG in both frequency and state-dependent manner.展开更多
基金supported by Technology Development and Research Projects of Ministry of Science and Scientific Research Institutes(NCSTE-2006-JKZX-293)Science and Technology Major Projects in Gansu Province(2009GS02443)National Science and Technology Support Program of China (2008BADB4B05)
文摘[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Method] The security of arecoline hydrobromide was evaluated based on acute toxicity tests; the ranges of safe medication, tolerability and toxicity as well as ＂Three-induced＇ effects （carcinogensis, mutagene- sis and teratogenesis） and reproductive toxicity were summarized according to the combinations of experimental results, papers and clinical effects. E Result] The results of acute toxicity tests in mice and rats showed that LD^0 （50% lethal dosages） of arecoline hydrobromide in mice was 691.83 mg/（kg.BW） and 95% incredible range of its LDso was 642.92 -744.47 mg/（ kg. BW）, and LDso of arecoline hydrobromide in rats was 2 054 mg/（kg.BW） and 95% incredible range of its LDso was 1 908 -2 210 mg/（kg.BW）. Its LDso value was hundreds times higher than the recommen- ded clinical dosage [ 1 -5 mg/（kg-BW） ], therefore it is safe to apply in clinic. The research results of ranges of safe medication, tolerability and toxicity showed that arecoline hydrobromide could entirely dispel the dog Diphyllobothrium, Spirometra mansoni, Dipylidium mesocestoides, Linea- tus and Cysticercus at dosages of 2 -3 mg/（ kg.BW）, and the same effects to Railletina tapeworm of chickens and Drepanidotaenia lanceolata of duck and goose at dosages of I -2 mg/（kg.BW）. The arecoline hydrobromide had muscarinic effects as side-effects and could cause vomiting, di- arrhea and other clinical symptoms to discharge the paralyzed worm from livestock body rapidly and completely. The arecoline hydrobromide had ＂Three-induced＂ effects and reproductive toxicity when it was used as antitapeworm drug with long-term, sustained and a large number of drug us- age, rather than used in clinical application with shorter time and lower dosage of administration. [ Conclusion] The arecoline hydrobromide is low- toxic substance and has a certain of toxicity such as ＂Three-induced＂ effects and reproductive toxicity at high-dosages application, and there are good effects on livestock and poultry tapeworm at the clinical recommended dosacles without ＂Three-induced＂ effects and reproductive toxicity.
基金supported by the Technology Development and Research Projects of Ministry of Science and Scientific Research Institutes(NCSTE-2006-JKZX-293)Science and Technology Major Projects in Gansu Province(2009GS02443)the National Science and Technology Support Program of China(2008BADB4B05)
文摘Taeniasis and cysticercosis in domestic animals belong to zoonosis and seriously threaten the public health security. Especially the cysticercosis and echinococcosis caused by the tapeworm eggs have great harms to bodies because they can attack many organs of body. According to the combination of experimental results and literature materials, the morphology and transmission mode of taenia and cysticercus, the prevalence status and monitoring of taeniasis and cysticercosis as well as the antitapeworm mechanism, comparative analysis to other drugs, expelling tapeworm tests in vitro, dose determining tests and usage notes of arecoline hydrobromide were expounded in detail. It provides a theoretical basis for prevention of taeniasis and cysticarcosis and more scientific usage of arecoline hydrobromide and thus relieves the harms of taeniasis and cysticercosis and ensuring the public health security.
基金This study was supported by the grants from the National Natural Science Foundation of China （No. 81170177 and No. 30770901 ）.Acknowledgment： We would like to thank Prof. Priori, University of Pavia in Italy for generously providing the hERG plasmid.
文摘Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K^＋ current （/hERG）. Methods Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the /hI=RG before and after the exposure to arecoline. Results Arecoline decreased the amplitude and the density of the /bERG in a concentration-dependent manner （IC5o=9.55 μmol/L）. At test potential of ＋60 mV, the magnitude of lhERG tail at test pulse of -40 mV was reduced from （151.7±6.2） pA/pF to （84.4±7.6） pA/pF （P 〈0.01, n=20） and the magnitude of IhERG tail at test pulse of -110 mV was reduced from （-187.5±9.8） pA/pF to （-97.6±12.6） pA/pF （P 〈0.01, n=20）. The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of IhERG was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of IhERG by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. Conclusion Arecoline could potently block IhERG in both frequency and state-dependent manner.
