| The mechanism of soman-induced seizure, especially in the prolonged time, has not been completely elucidated; and the therapy of seizure also has been an unsolved problem for the globally chemical weapon defence research. So, the propose of our study is, to exploit novel drugs to control the seizure, especially in the prolonged time; and investigate the mechanism of the anticonvulsant action of drugs so as to perfect the mechanism of seizure.The onset of soman-induced seizure results from the derangement of cholinergic system, so the anticholinergic drugs have long been known to elicit protection against the seizure. Research from Professor Liu Chuanggui and others in our institute found that, compared with muscarine (M) receptor antagonist used by foreign armies against seizure, the drugs which act on both M and nicotine (N) receptors had better anticonvulsant effects in the early phase of soman-induced seizure. But, can these above-mentioned drugs also execute their anticonvulsant effects in the prolonged time of seizure? If there is,how the anticholinergic drug(act on M and N receptor)works? In order to answer these questions, we first established the model of soman-induced seizure in rat, compared the anticonvulsant effects of the specially M receptor antagonists with the anticonvulsant actions of 8021 and other drugs which act on both M and N receptors. On the base of this work, further investigation was to elucidate the anticonvulsant mechanism by pharmacological, neurochemical and electrophysiological methods. The main results are summarized as follows:1 The anticonvulsant effects of different anticholinergic drugs when administrated in different phase of soman-induced seizureOn the base of the establishment of the model of soman-induced seizure in rat, we evaluate the anticonvulsant efficiency of 8021 and other anticholinergic drugs which act on M receptor or both M and N receptors in different phase since seizure onset. The results show all the anticholinergic drugs, including the M receptor antagonist atropine (20mg.kg-1ip), and the M and N receptor antagonists including scopolamine (2mg.kg-1ip), 8018 (4mg.kg-1ip), benactyzine (6 mg'kg-1ip) and 8021(4mg.kg-1ip), can executive their good anticonvulsant effectiveness when administrated at 5 min since seizure-onset. But , compared with other anticonvulsant drugs, larger dose was required for atropine to terminate the seizure. At 20min since seizure-onset, all theanticholinergic drugs apart from atropine, which lost its anticonvulsant effectiveness even the dose was increased to 60mg.kg-1, could also control the seizure; Besides, at this phase, although scopolamine can terminate the seizure, the dose increased significantly(from 2 to 8 mg'kg-1 ip); at 40min since seizure-onset, scopolamine and 8018 were not capable of terminating the seizure even the dose increased to 60mg.kg-1 ip ( scopolamine) and 40 mg'kg-1 ip (8018), and the animals showed signs of poisoning by large doses of anticholinergic drugs; but unlike scopolamine and 8018 , 8021 and benactyzine could also pause the ongoing seizure with the small increasing dose(8mg'kg-1 ip for 8021 and 10 mg'kg-1 ip for benactyzine).As for the time taken to control seizure, at 5min since seizure-onset, atropine took longer time to terminate the seizure than other anticholinergic drugs; at 20min since seizure-onset, compared with 8018 and scopolamine, 8021 and benactyzine took less time to stop the ongoing seizure. Furthermore, the time taken by scopolamine and 8018 to pause the seizure increased with the administrated time; but the time taken to terminate the seizure of the 8021 and benactyzine didn't vary with the time of administration.The above-mentioned results suggest that the anticonvulsant action of 8021 and benactyzine may be different from the special M receptor antagonist atropine, and also from the M and N receptor antagonists such as 8018 and scopolamine, so we can conclude that the good anticonvulsant effectiveness of 8021 and benactyzine in the prolonged time of seizure may be...
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