Sarcosine, a natural
amino acid found in muscles and other body tissues, is an endogenous
glycine transporter type 1 inhibitor that increases the
glycine concentration, resulting in an indirect potentiation of the
N-methyl-D-aspartate (
NMDA) subtype of
glutamate receptors.
Sarcosine, similar to other
NMDA receptor-activating agents, is an effective adjuvant in the treatment of
schizophrenia. It is widely accepted that increased glutamatergic neurotransmission is involved in the initiation and propagation of
seizures. Because
sarcosine facilitates
NMDA receptor function, it may affect the seizure threshold. Therefore, we examined the effects of
sarcosine on the seizure threshold in two different mouse seizure models: the timed intravenous (iv)
pentylenetetrazole (PTZ) infusion test and the maximal electroshock seizure threshold test. In the iv PTZ test,
sarcosine did not exert a significant effect on the seizure threshold at any of the doses tested (100, 200, 400 and 800 mg/kg, ip). However, at doses of 400 and 800 mg/kg,
sarcosine significantly raised the threshold for electroconvulsions (p < 0.01). The present findings indicate that
sarcosine did not lower the seizure threshold. Conversely,
sarcosine showed weak
anticonvulsant properties by increasing the threshold current for the induction of
tonic seizures. Therefore,
sarcosine may be considered as a safe adjuvant treatment for
schizophrenia without proconvulsant risk. In addition, the compound may serve as an interesting addition to
epilepsy treatment.