INTERACTIONS OF PENTAMETHYLENETETRAZOLE AND TETRAZOLE ANALOGS WITH THE PICROTOXININ SITE OF THE BENZODIAZEPINE-GABA RECEPTOR-IONOPHORE COMPLEX
INTERACTIONS OF PENTAMETHYLENETETRAZOLE AND TETRAZOLE ANALOGS WITH THE PICROTOXININ SITE OF THE BENZODIAZEPINE-GABA RECEPTOR-IONOPHORE COMPLEX
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DOI：
10.1016/0014-2999(84)90282-6
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发表时间：
1984-01-01
影响因子：
5
通讯作者：
TICKU, MK
中科院分区：
文献类型：
--
作者：
RAMANJANEYULU, R;TICKU, MK
本文研究了五亚甲基四氮唑和10-四唑类似物[6，6‘-二氯五亚甲基、L-环己基-5-甲基、7-甲基-10-异丙基五亚甲基、7-甲基-9-异丙基五亚甲基、7-甲基-9-异丙基五亚甲基、6-邻氯苯基、1-异丁基-5-亚甲基、1-甲基-5-环己基-8-亚甲基]与苯二氮卓-GABA受体-离子载体复合体的微毒素部位的相互作用。所有活性的TTZ类似物都有效地抑制了与苦参素结合的配体[35S]叔丁基双环硫代磷酸盐(TBPT)的结合。TTZ类似物似乎与印防己毒素位点竞争性地相互作用。所有受试的TTZ类似物对TBPT结合的抑制作用均强于地西潘结合。在抑制TBPT结合的TTZ类似物与它们引起惊厥的剂量之间有相当好的相关性。五亚甲基TTZ在类似于该药物引起的惊厥期间的体内浓度的浓度下抑制TBPT的结合。因此，TTZ可能通过作用于苯二氮卓类-GABA受体-离子载体复合体的印防己毒素敏感部位而引起惊厥。
The interactions of pentamethylenetetrazole and 10-tetrazole [TTZ] analogs [6,6''-dichloropentamethylene TTZ, l-cyclohexyl-5-methyl-TTZ, 7-methyl-10-isopropylpentamethylene TTZ, 7-methylpentamethylene TTZ, 7-methyl-9-isopropylpentamethylene TTZ, heptamethylene TTZ, 6-o-chlorophenyl TTZ, 1-isobutyl-5-methylene TTZ, 1-methyl-5-cyclohexyl TTZ octamethylene TTZ] with the picrotoxinin site of the benzodiazepine-GABA receptor-ionophore complex was investigated [in rats]. All the active TTZ analogs potently inhibited the binding of [35S]tert-butyl-bicyclophosphorothionate (TBPT), a ligand which binds to the picrotoxinin site. TTZ analogs appear to interact with the picrotoxinin site competitively. All the TTZ analogs tested were more potent in inhibiting TBPT binding than diazepam binding. There is a reasonably good correlation between the TTZ analogs to inhibit TBPT binding and the doses at which they produce convulsions. Pentamethylene TTZ inhibited TBPT binding at concentrations which are similar to the in vivo concentrations present during convulsions produced by this drug. Thus, TTZ may produce convulsions by acting at the picrotoxin-sensitive site of the benzodiazepine-GABA receptor-ionophore complex.