iloprost and Seizures

A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH

Topics: Amino Alcohols; Animals; Anticonvulsants; Crystallography, X-Ray; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Mice; Models, Molecular; Molecular Structure; Rats; Seizures; Structure-Activity Relationship

The effects of iloprost, a chemically stable analog of prostacyclin, on motor activity, pentylenetetrazol (PTZ)- and strychnine (ST)-induced seizures were studied in rats. Depression on motor activity was observed after a 500 ng/icv dose. Thus, both spontaneous locomotor activity and exploratory behavior were significantly reduced. While iloprost was ineffective against ST-induced seizures, it produced dose-dependent inhibition of PTZ-induced seizures. ED50 (95% confidence limits) value of iloprost for the suppression of clonic convulsions induced by PTZ was 224.96 (100.43-504.00) ng/icv. Anticonvulsive effect of iloprost was significantly potentiated by clonazepam pretreatment. In this case ED50 of iloprost was 39.40 (23.88-65.01) ng/icv. Unilateral iloprost injections into substantia nigra pars reticulata in a relatively lower dose range (0.5-2.0 ng/ic) also dose-dependently inhibited PTZ-induced seizures. In comparison to other prostanoids iloprost seems to have more potent and selective anticonvulsive activity against PTZ-induced seizures without marked motor depressant action in rats. It is further suggested that antiseizure effect of iloprost might be mediated by GABAergic inhibitory mechanisms.

Topics: Animals; Clonazepam; Iloprost; Injections, Intraventricular; Male; Motor Activity; Rats; Seizures

The effects of iloprost (ZK 36,374), a new chemically stable analogue of prostacyclin (PGI2), on strychnine-, pentylene-tetrazol-, and maximal electroshock-induced seizures were studied in mice. The time from the beginning of the injection of the convulsant or inducing electroshock to the stage of persistent seizures was determined, and lack of tonic hindlimb extension was regarded as inhibition of convulsions. In doses of 8 micrograms--16 micrograms kg-1 iloprost already exhibited an anticonvulsant action by markedly reducing the incidence of seizures and mortality following strychnine, pentylenetetrazol or maximal electroshock. The onset of tonic seizures was also reduced by iloprost. PGE1 and PGI2 were generally effective in 7 to 13 times higher doses than iloprost. It is suggested that the anticonvulsant activity of iloprost, PGE1 and PGI2 might involve a common basic mechanism. Due to its efficacy, iloprost is a useful tool in the investigation of the anticonvulsant action of prostaglandins.

Topics: Alprostadil; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Electroshock; Epoprostenol; Iloprost; Male; Mice; Seizures