Smith S E, Dürmüller N
Department of Neurology, Institute of Psychiatry, Denmark Hill, London, U.K.
Eur J Pharmacol. 1990 Dec 4;191(3):337-43. doi: 10.1016/0014-2999(90)94166-u.
The effect of i.c.v. administration of dodecasodium and dicalcium inositolhexakisphosphate (Na12IP6 and Ca2IP6, respectively) to mice and rats was studied. In mice, Na12IP6 (1-300 nmol) or Ca2IP6 (10-500 nmol) induced: ataxia, ground-hugging, tremor (often continuous), scratching, hyperlocomotion, wild running, myoclonic jerks, jumping, clonic muscle spasms, tonic seizure, followed by death or full recovery. The CD50 values for clonic seizures for Na12IP6 and Ca2IP6 were 16 and 49 nmol, respectively. The convulsant effect of Na12IP6 (15 nmol i.c.v.) was not blocked by pretreatment with D(-)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylate, but was dose dependently reduced by pretreatment with CaCl2 (30-60 nmol i.c.v.) and abolished by coadministration of CaCl2 (30 nmol) with Na12IP6 (i.c.v.). In rats, Na12IP6 (50 nmol i.c.v.) induced severe electroencephalographic seizures in the hippocampus and cortex. The potent convulsant effect of IP6 (administered i.c.v.) depends at least in part on a calcium-chelating action.
研究了向小鼠和大鼠脑室内注射十二钠肌醇六磷酸（分别为Na12IP6）和二钙肌醇六磷酸（Ca2IP6）的效果。在小鼠中，Na12IP6（1 - 300纳摩尔）或Ca2IP6（10 - 500纳摩尔）会引发：共济失调、贴地爬行、震颤（常为持续性）、抓挠、运动亢进、狂奔、肌阵挛性抽搐、跳跃、阵挛性肌肉痉挛、强直性惊厥，随后死亡或完全恢复。Na12IP6和Ca2IP6阵挛性惊厥的半数惊厥剂量（CD50）值分别为16和49纳摩尔。D(-)-4-(3-膦酰基-2-丙烯基)-哌嗪-2-羧酸预处理不能阻断Na12IP6（脑室内注射15纳摩尔）的惊厥作用，但氯化钙（脑室内注射30 - 60纳摩尔）预处理可使其惊厥作用呈剂量依赖性降低，且氯化钙（30纳摩尔）与Na12IP6（脑室内注射）共同给药可消除该作用。在大鼠中，Na12IP6（脑室内注射50纳摩尔）可在海马体和皮质诱发严重的脑电图癫痫发作。IP6（脑室内注射）的强效惊厥作用至少部分取决于其钙螯合作用。
