Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic ...Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1：4, 1 ：1, 4：1, were evaluated in maximal electroshock （MES）-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss＇s method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices （BI） for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography （HPLC）. Results Combinations of PTA and UTA at the ratio of 4：1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 ：4 and 1 ： 1, despite synergistic in MES test, were additive in acute toxicity test. The 4：1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4：1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4：1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.展开更多
Objective: To evaluate the serious response during tilt-table test (TTT) and its prophylactic management. Method: Seventy-six elderly patients were tested at a tilt angle of 70 degrees for a maximum of 45 min and then...Objective: To evaluate the serious response during tilt-table test (TTT) and its prophylactic management. Method: Seventy-six elderly patients were tested at a tilt angle of 70 degrees for a maximum of 45 min and then subjected to isoprotere- nol-provocative tilt testing. ECG and blood pressure were monitored during the test and patients were kept at normal saline con- dition through a peripheral intravenous duct. Results: Fifty-one of 76 patients were defined as positive including 23 having serious response; 6 of the 23 patients had arteriosclerosis involving internal carotid arteries and 7 cases had bradycardia, two of which were associated with II°-I A-V block and the others with chronic atrial fibrillation. The serious response consisted of cardiac arrest for more than 5 s (6 cases), or serious bradycardia for more than 1 min (7 cases) or serious hypotension for more than 1 min (10 cases). Those with serious response were managed by returning to supine position, thus driving up legs and intravenous atropine, CPR (2 cases with cardiac arrest) and needing oxygen supplementation (11 cases). Only 2 hypotension patients recovered gradually by 10 min after emergency management, while others recovered rapidly with no complications. Conclusion: Although non-invasive, TTT may result in serious response, especially in elderly. Therefore proper patient selection, control of isoproterenol infusion and close observation of vital signs are decisive for a safe consequence.展开更多
Objective: to evaluate cilazapril in vasovagal syncope treatment. Method: eighty\|six cases of VVS patients found positive in TTT tilt were medicated with 2.5 mg cilazapril daily for three months and followed up by TT...Objective: to evaluate cilazapril in vasovagal syncope treatment. Method: eighty\|six cases of VVS patients found positive in TTT tilt were medicated with 2.5 mg cilazapril daily for three months and followed up by TTT. Results: seven cases quit due to cough or unexplained reason; 79 VVS patients had no more fainting spells; 75.95% of TTT results of patients changed to negative after 3 months therapy. The before and after cilazapril treatment average blood pressures (taken in lying position) were 121/73 mm Hg (1 mm Hg= 0.133kPa) and 120/76 mm Hg respectively ( P > 0.05); and mean heart rates were 68.63±12.37/min and 70.13±13.15/min respectively with no significant changes ( P > 0.05). Conclusion: Cilazapril was effective in treatment of VVS; did not affect normal blood pressure and heart rate; was safe; and had little side effect.展开更多
In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a^5f were synthesized by condensation of various benzils 4a^4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and...In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a^5f were synthesized by condensation of various benzils 4a^4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies. Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectroscopic data.展开更多
Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All th...Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.展开更多
基金Natural Science Foundation of Shanxi Province(No 20041109).
文摘Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1：4, 1 ：1, 4：1, were evaluated in maximal electroshock （MES）-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss＇s method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices （BI） for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography （HPLC）. Results Combinations of PTA and UTA at the ratio of 4：1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 ：4 and 1 ： 1, despite synergistic in MES test, were additive in acute toxicity test. The 4：1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4：1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4：1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.
文摘Objective: To evaluate the serious response during tilt-table test (TTT) and its prophylactic management. Method: Seventy-six elderly patients were tested at a tilt angle of 70 degrees for a maximum of 45 min and then subjected to isoprotere- nol-provocative tilt testing. ECG and blood pressure were monitored during the test and patients were kept at normal saline con- dition through a peripheral intravenous duct. Results: Fifty-one of 76 patients were defined as positive including 23 having serious response; 6 of the 23 patients had arteriosclerosis involving internal carotid arteries and 7 cases had bradycardia, two of which were associated with II°-I A-V block and the others with chronic atrial fibrillation. The serious response consisted of cardiac arrest for more than 5 s (6 cases), or serious bradycardia for more than 1 min (7 cases) or serious hypotension for more than 1 min (10 cases). Those with serious response were managed by returning to supine position, thus driving up legs and intravenous atropine, CPR (2 cases with cardiac arrest) and needing oxygen supplementation (11 cases). Only 2 hypotension patients recovered gradually by 10 min after emergency management, while others recovered rapidly with no complications. Conclusion: Although non-invasive, TTT may result in serious response, especially in elderly. Therefore proper patient selection, control of isoproterenol infusion and close observation of vital signs are decisive for a safe consequence.
文摘Objective: to evaluate cilazapril in vasovagal syncope treatment. Method: eighty\|six cases of VVS patients found positive in TTT tilt were medicated with 2.5 mg cilazapril daily for three months and followed up by TTT. Results: seven cases quit due to cough or unexplained reason; 79 VVS patients had no more fainting spells; 75.95% of TTT results of patients changed to negative after 3 months therapy. The before and after cilazapril treatment average blood pressures (taken in lying position) were 121/73 mm Hg (1 mm Hg= 0.133kPa) and 120/76 mm Hg respectively ( P > 0.05); and mean heart rates were 68.63±12.37/min and 70.13±13.15/min respectively with no significant changes ( P > 0.05). Conclusion: Cilazapril was effective in treatment of VVS; did not affect normal blood pressure and heart rate; was safe; and had little side effect.
文摘In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a^5f were synthesized by condensation of various benzils 4a^4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies. Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectroscopic data.
文摘Objective: A series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. Methods: All the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Results: A majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens. Conclusion: The results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.
