Effects of sarcosine, a glycine transporter type 1 inhibitor, in two mouse seizure models.

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.

Anticonvulsant activity and tolerance of ELB138 in dogs with epilepsy: a clinical pilot study.

A new antiepileptic and anxiolytic drug, ELB138, was evaluated in a clinical pilot study in dogs with newly diagnosed or chronic idiopathic epilepsy. The purpose was to verify clinically the anticonvulsant effectiveness of this substance, which had already been demonstrated experimentally. Data from 29 dogs treated with ELB138 were compared with results obtained retrospectively from 82 dogs treated with conventional antiepileptic medication. The reduction in seizure frequency using ELB138 in dogs with newly diagnosed idiopathic epilepsy was comparable to the reduction in dogs treated either with phenobarbital or primidone. In dogs with chronic epilepsy and add-on therapy with either ELB138 or potassium bromide, such supplementation reduced the seizure frequency and the duration and severity of seizures. The most obvious difference between ELB138 treatment and conventional medications became clear in the evaluation of side effects, which in those dogs treated with ELB138 were rare, and consisted mostly of transient polyphagia. This pilot study confirmed that ELB138 has a potent anticonvulsant effect in dogs with idiopathic epilepsy. These results will form the basis for a multicentre, blinded study.