Effects of sarcosine, a glycine transporter type 1 inhibitor, in two mouse seizure models.
Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 2
Abstract
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.
Authors and Affiliations
Katarzyna Socała, Dorota Nieoczym, Chris Rundfeldt, Piotr Wlaź
Keywords
Related Articles
- EP ID EP102454
- DOI -
- Views 103
- Downloads 0
Effect of quercetin on experimental hyperlipidemia and atherosclerosis in rabbits.
Cardiovascular disease is currently the leading cause of death in the West, and a search for factors limiting its occurrence is ongoing. Accumulated data indicate that quercetin, the major flavonol in the plant kingdom,...
Analgesic and anti-inflammatory activity of stereoisomers of carane derivatives in rodent test.
Our previously conducted pharmacological investigations led us to discovery of the strong local anesthetic activity of the compound KP-23RS. The following studies revealed that its R- and S-diasteroisomers had different...
Mechanism of action of clozapine in the context of dopamine D(1)-D(2) receptor hetero-dimerization - a working hypothesis.
The tight correlation between the clinical potency and the D(2)R blocking action of antipsychotic medications suggests that dopamine hyperactivity plays a significant role in psychosis. Clozapine, one of the most effecti...
Ebselen attenuates oxidative stress in ischemic astrocytes depleted of glutathione. Comparison with glutathione precursors.
In this study, we investigated the protective effect of ebselen, a seleno-organic compound with antioxidant activity, towards astrocyte degeneration caused by exposure to simulated in vitro ischemic conditions and simult...
Professor Ullrich Trendelenburg, M.D., Ph.D. (1922–2006). Obituary.