Behavioral and in vitro evaluation of tetrodotoxin tolerability for therapeutic applications
- 作者：Lidia Morales ; Carmen Pé ; rez-Garcí ; a ; Elisabet Salas ; Carmen Gonzá ; lez-Martí ; n ; Carmen Castillo ; Maria José ; Polanco ; Gonzalo Herradó ; n ; Luis Fern ; o Alguacil
- 关键词：Tetrodotoxin ; Place conditioning ; Cytotoxicity ; HepG2
- 刊名：Toxicon
- 出版年：2008
- 期刊代码：50_00410101
- 类别：pha
- 出版时间：15 June 2008
- 卷：51
- 期：8
- 页码：1530-1534
- 文件大小：493 K
摘要
Tetrodotoxin (TTX) injection is currently being studied in clinical trials for potential antinociceptive applications. This work tries to increase the knowledge of its biological tolerability by using a behavioral procedure that can detect aversive effects of drug treatments, as well as in vitro cytotoxicity studies in non-excitable cell systems. Place conditioning studies with Sprague-Dawley male rats showed that pharmacologically active TTX injections (2.5 μg/kg, subcutaneous) were devoid of negative reinforcing properties, the drug being able to prevent the aversive effect of the vehicle. Similarly, TTX was not cytotoxic by itself as evaluated with the neutral red test and the MTT assay in HepG2 cells incubated for 24 h with TTX concentrations as high as 400 μM. The results support the idea that low doses of TTX can be well tolerated.