Inositolhexakisphosphate is convulsant in mice and rats in the nanomolar range

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.