Aripiprazole is an
antipsychotic drug which acts through
dopamine and
serotonin receptors.
Aripiprazole was noted to have antiseizure effects in a study on mice, while it induced
seizures in a few human case reports. Dopaminergic and serotonergic systems relate to
nitric oxide, and
aripiprazole also has effects on
dopamine and
serotonin receptors. This study investigated the effects of
aripiprazole on
seizures and the potential role of
nitric oxide in the process. The following three models were examined to explore the role of
aripiprazole on
seizures in mice: 1 -
pentylenetetrazole administered intravenously, 2 -
pentylenetetrazole administered intraperitoneally, and 3 - electroshock.
Aripiprazole administration delayed clonic seizure in intravenous and intraperitoneal
pentylenetetrazole models. In the electroshock-induced seizure model, tonic seizure and mortality protection percent were increased after
aripiprazole administration. In intraperitoneal administration of
pentylenetetrazole,
aripiprazole effects on clonic seizure latency were significantly decreased when
l-NAME - a nonselective
nitric oxide synthase (NOS) inhibitor,
7-nitroindazole - a selective neuronal NOS (nNOS) inhibitor, or
aminoguanidine - a selective inducible NOS (iNOS) inhibitor was injected before
aripiprazole administration. In the intravenous
pentylenetetrazole method, administration of
l-NAME or
aminoguanidine inhibited
aripiprazole effects on clonic seizure threshold.
Aminoguanidine or
l-NAME administration decreased
aripiprazole-induced protection against
tonic seizures and death in the electroshock model. In both intravenous and intraperitoneal seizure models,
aripiprazole and
l-arginine coadministration delayed the onset of
clonic seizures. Moreover, it increased protection against
tonic seizures and death in intraperitoneal
pentylenetetrazole and electroshock models. In conclusion, the release of
nitric oxide via iNOS or nNOS may be involved in
anticonvulsant properties of
aripiprazole.