Behavioral and in vitro evaluation of tetrodotoxin tolerability for therapeutic applications.
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 microg/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 24h with TTX concentrations as high as 400 microM. The results support the idea that low doses of TTX can be well tolerated.
Morales
Lidia
L
Servicio de Farmacología y Toxicología Experimental (SFT-SAI), Universidad San Pablo-CEU, Boadilla del Monte, Madrid, Spain.
Pérez-García
Carmen
C
Salas
Elisabet
E
González-Martín
Carmen
C
Castillo
Carmen
C
Polanco
Maria José
MJ
Herradón
Gonzalo
G
Alguacil
Luis Fernando
LF
D000700:Analgesics / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D045744:Cell Line, Tumor; D003213:Conditioning, Psychological; D003603:Cytotoxins / Q000633:toxicity*; D006801:Humans; D008297:Male; D014677:Pharmaceutical Vehicles / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000633:toxicity*
D000700:Analgesics; D003603:Cytotoxins; D014677:Pharmaceutical Vehicles; D013779:Tetrodotoxin