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Sample records for benactyzine

  1. Effects of benactyzine on action potentials and contractile force of guinea pig papillary muscles

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Aim:To explore the effects of benactyzine (BEN) on the action potential and contractile force in guinea pig papillary muscles.Methods:Conventional microelectrode technique was used to record the fast action potentials (FAP) and slow action potentials (SAP) of guinea pig papillary muscles.Results:Benactyzine 5,10,50 μmol·L-1 suppressed the maximal upstroke velocity (vmax) of FAP and contractile force (Fc) concentration-dependently while prolonged the action potential duration at 50%,90% repolarization (APD50,APD90) and effective refractory period (ERP) of FAP.The suppression on the vmax was frequency-dependent.Benactyzine 5,10,50μmol·L-1 lengthened the APD50,APD90 of SAP induced by isoprenaline or histamine when perfused with KCl 22 mmol·L-1 Tyrode's solution.The vmax of the SAP was not decreased by benactyzine 5,10 μmol·L-1 but by 50 μmol·L-1.The effects on the SAP were antagonized by elevation of the extracellular calcium from 2.0 to 5.6 mmol·L-1.The effects of benactyzine on SAP elicited by tetrodotoxin resembled that by isoprenaline or histamine except the more pronounced suppression on vmax and action potential amplitude (APA).The persistent rapid spontaneous activity and triggered tachyarrhythmia induced by ouabain were also abolished immediately by benactyzine 5 μmol·L-1.Conclusion:Benactyzine can inhibit Na+,K+,Ca2+ transmembrane movement and intracellular Ca2+ mobilization in the myocardium,and this may be the electrophysiological basis of its effects against experimental arrhythmias.

  2. Investigation of Visual Performance after Administration of Cholinergic Blocking Agents. I. Benactyzine.

    Science.gov (United States)

    1980-03-01

    that the drug was ineffective. Himwich and Rinaldi (1957) noted that benactyzine improved Parkinson -like symptoms in 9 of 13 patients studied, and that...L.F., and Gillespie, H.K. (1971). Marihuana and the temporal span of awareness. Arch. Gen. Psychiat.,24,564-567. Masland, R.H. (1979) in Symposium 106

  3. 贝那替秦对最大电休克发作模型和戊四氮惊厥发作阈模型小鼠的抗惊厥作用%Anticonvulsant effects of benactyzine on maximal electroshock seizure and pentetrazole seizure threshold test model mice

    Institute of Scientific and Technical Information of China (English)

    陈小飞; 李建雄; 王永安

    2011-01-01

    目的 评价贝那替秦等抗胆碱药在不同惊厥模型的抗惊厥疗效,探讨其可能的作用机制.方法 通过ig给予贝那替秦2~40 mg·kg-1记录最大电休克发作模型( MES)及戊四氮惊厥发作阈模型(MST)模型小鼠的未出现惊厥数.制备新生Wistar小鼠海马神经元细胞,加入贝那替秦1~100 μmol·L-1,MTT检测细胞存活率.结果 贝那替秦2~40 mg·kg-1在MES模型未出现惊厥数为2/10~7/10,在MST模型上未出现惊厥数为1/10~9/10均明显高于模型组(P<0.05,P<0.01),2个模型的ED50分别为12.2(4.7~53.6)mg·kg-1和12.5(7.0~25.9)mg·kg-1.贝那替秦1~100 μmol·L-1能明显对抗N-甲基-D-天冬氨酸(NMDA)对海马神经元的损伤作用,细胞存活率明显增加(P<0.05).结论 贝那替秦在MES及MST惊厥模型均具明显抗惊厥作用,其作用机制可能与其对NMDA受体的拮抗作用有关.%OBJECTIVE To evaluate the anticonvulsant effect of benactyzine and other anticholinergic drugs on different seizure models and investigate their anti-seizure mechanism. METHODS Benactyzine 2 -40 mg· kg -1 were given ig to mice. The number of mice without convulsant appearance was recorded in the maximal electroshock seizure (MES) and pentetrazole (Metrazol)seizure threshold test (MST) model. Benactyzine 1 -100 μmol·L-1 was added to primary cultured hippocampus neurons, and the cell survival was detected by MTT assay. RESULTS The number of mice without convulsant appearance was 2/10 -7/10 in the MES model vs 1/10 -9/10 in MST model. The ED50 of benactyzine in MES model was 12.2 (4.7 - 53.6) mg· kg-1 vs 12.5 (7.5 -25.9)mg·kg-1 in the MST model. The cell survival in benactyzine 1 -100 μmol·L-1 group was significantly higher than that of N-methyl-D-aspartic acid ( NMDA ) model group ( P < 0.05 ).CONCLUSION Benactyzine shows significant anti-seizure effect on both MES and MST. The anticonvulsant mechanism might be related to its antagonism against NMDA receptors.

  4. Anticholinergic drugs--functional antidotes for the treatment of tabun intoxication.

    Science.gov (United States)

    Krejcová, Gabriela; Kassa, Jirí

    2004-01-01

    1. To study the influence of antidotes on tabun-induced neurotoxicity, the rats were injected intramuscularly with organophosphate tabun (LD50). The efficacy of choice antidotal treatment consisting of acetylcholinesterase reactivator obidoxime and one of four anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) was compared. 2. Testing of tabun-induced neurotoxicity progress was carried out using the method Functional observational battery. The experimental animals as well as controls were observed at 24 hours and 7 days following tabun or saline administration. 3. The results were compared to the condition of animals without anticholinergic drug (oxime alone) and control rats that received physiological solution instead of tabun and treatment. Antidotal treatment involving centrally acting anticholinergic drugs (benactyzine, biperiden, scopolamine) showed significantly higher neuroprotective efficacy compared to antidotal treatment containing atropine.

  5. Anticonvulsant actions of anticholinergic drugs in soman poisoning. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Capacio, B.R.; Shih, T.M.

    1991-12-31

    The acute effects of the organophosphorus cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds, aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, biperiden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman-induced hypersecretions and convulsions. Male rats were injected with the oxime HI-6 (125 mg/kg, i.p.), to increase survival time, along with various intramuscular doses of the anticholinergics 30 min prior to a dose of soman that produced 100% convulsions. Signs of intoxication as well as the time-to-onset of convulsions were observed. The calculated anticonvulsant median effective dose values were 0.18, 0.33, 0.36, 0.55, 2.17, 2.30, 2.45, and 31.09 micro mol per kilogram for scopolamine HBr, biperiden, trihexyphenidy, benactyzine, benztropine, azaprophen, aprophen, and atropine sulfate, respectively. The same rank order by potency for inhibition of hypersecretions among these compounds was observed.

  6. Therapy against organophosphate poisoning: the importance of anticholinergic drugs with antiglutamatergic properties.

    Science.gov (United States)

    Weissman, Ben Avi; Raveh, Lily

    2008-10-15

    Potent cholinesterase inhibitors (e.g., soman, sarin), induce a wide range of deleterious effects including convulsions, behavioral impairments and ultimately, death. Due to the likelihood of various scenarios of military or terrorist attacks by these and other chemical weapons, research has to be aimed at finding optimal therapies. Early accumulation of acetylcholine in synaptic clefts was suggested to trigger an array of toxic events including an excessive release of glutamate, culminating in the activation of its receptors. Stimulation of the N-Methyl-D-Aspartate (NMDA) subtype of these receptors was associated with the neuronal injury that initiates organophosphate-induced brain damage. The notion of a stepwise mechanism yielded treatments based on a combination of an immediate administration of enzyme reactivators and anticholinergic drugs. This strategy dramatically increased survival rates but did not abolish convulsions and failed to prevent the ensuing cognitive dysfunction. Efforts to improve this paradigm by adding anticonvulsants or antiglutamatergic drugs with anti-epileptic characteristics produced dubious results. Under these conditions, benactyzine and caramiphen, agents with anticholinergic and antiglutamatergic properties, provided improved protection when introduced as adjunct agents to oximes, reversible cholinesterase inhibitors and/or specific antimuscarinic drugs such as atropine. In contrast, the specific antimuscarinic drug scopolamine failed to block soman-induced changes in glutamatergic and behavioral parameters even when given prophylactically. These findings along with a large number of additional reports led towards the conclusion that the therapeutic advantage of drugs such as benactyzine and caramiphen could derive from their ability to modulate central cholinergic and glutamate neurotransmission.

  7. Study of the n-methyl-d-aspartate antagonistic properties of anticholinergic drugs

    Energy Technology Data Exchange (ETDEWEB)

    McDonough, J.H.; Shih, T.M.

    1995-12-31

    A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs. PHARMACOL BIOCHEM BEHAV. 51(2/3) 249-253, 1995. Drugs that act at the N-methyl-D-aspartate (NMDA) receptor complex have the ability to terminate nerve agent-induced seizures and modulate the neuropathologic consequences of agent exposure. Drugs with mixed anticholinergic and anti-NMDA properties potentially provide an ideal class of compounds for development as anticonvulsant treatments for nerve agent casualties. The present experiment evaluated the potential NMDA antagonist activity of 11 anticholinergic drugs by determining whether pretreatment with the compound was capable of protecting mice from the lethal effects of NMDA. The following anticholinergic drugs antagonized NMDA lethality and are ranked according to their potency: mecamylamine > procyclidine = benactyzine > biperiden > tribexyphenidyl. The anticholinergics atropine, aprophen, azaprophen, benztropine, 3-quinudidinyl benzilate (QNB), and scopolamine failed to show NMDA antagonist properties. In addition, and unexpectedly, diazepam, ethanol, and pentobarbital were also shown to be capable of antagonizing NMDA lethality over a certain range of doses. The advantages and limitations of using antagonism of NMDA lethality in mice as a bioassay for determining the NMDA antagonist properties of drugs are also discussed.

  8. A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice.

    Science.gov (United States)

    Kassa, Jirí; Vachek, J

    2002-08-15

    The ability of two types of pharmacological pretreatment (pyridostigmine alone or pyridostigmine in combination with two anticholinergic drugs) to increase the resistance of rats and mice against tabun and to increase the therapeutic efficacy of common antidotal treatment of tabun-poisoned rats and mice was compared. A significant decrease in the LD50 values of tabun was observed when mice as well as rats were pretreated with the prophylactic antidotal mixture consisting of pyridostigmine, benactyzine and trihexyphenidyle, designated PANPAL. Pyridostigmine-pretreated rats were also more resistant against acute lethal effects of tabun but pyridostigmine-induced resistance of rats was not so high as PANPAL-induced resistance. In addition, the pharmacological pretreatment with pyridostigmine alone was not able to protect mice against tabun-induced acute toxicity. The pharmacological pretreatment with pyridostigmine alone was able to increase the efficacy of currently used antidotal treatment (obidoxime in combination with atropine and diazepam) of tabun-induced poisoning, but PANPAL-induced increase in the efficacy of the same antidotal treatment was significantly higher than an increase induced by pyridostigmine alone. PANPAL-induced increase in the efficacy of antidotal treatment of tabun poisoning was also observed in mice. These findings confirm that PANPAL pretreatment of tabun-poisoned rats and mice seems to be much more suitable than currently used pyridostigmine alone.

  9. Advances in toxicology and medical treatment of chemical warfare nerve agents

    Directory of Open Access Journals (Sweden)

    Moshiri Mohammd

    2012-11-01

    Full Text Available Abstract Organophosphorous (OP Nerve agents (NAs are known as the deadliest chemical warfare agents. They are divided into two classes of G and V agents. Most of them are liquid at room temperature. NAs chemical structures and mechanisms of actions are similar to OP pesticides, but their toxicities are higher than these compounds. The main mechanism of action is irreversible inhibition of Acetyl Choline Esterase (AChE resulting in accumulation of toxic levels of acetylcholine (ACh at the synaptic junctions and thus induces muscarinic and nicotinic receptors stimulation. However, other mechanisms have recently been described. Central nervous system (CNS depression particularly on respiratory and vasomotor centers may induce respiratory failure and cardiac arrest. Intermediate syndrome after NAs exposure is less common than OP pesticides poisoning. There are four approaches to detect exposure to NAs in biological samples: (I AChE activity measurement, (II Determination of hydrolysis products in plasma and urine, (III Fluoride reactivation of phosphylated binding sites and (IV Mass spectrometric determination of cholinesterase adducts. The clinical manifestations are similar to OP pesticides poisoning, but with more severity and fatalities. The management should be started as soon as possible. The victims should immediately be removed from the field and treatment is commenced with auto-injector antidotes (atropine and oximes such as MARK I kit. A 0.5% hypochlorite solution as well as novel products like M291 Resin kit, G117H and Phosphotriesterase isolated from soil bacterias, are now available for decontamination of NAs. Atropine and oximes are the well known antidotes that should be infused as clinically indicated. However, some new adjuvant and additional treatment such as magnesium sulfate, sodium bicarbonate, gacyclidine, benactyzine, tezampanel, hemoperfusion, antioxidants and bioscavengers have recently been used for OP NAs poisoning.