Tenocyclidine treatment in soman-poisoned rats--intriguing results on genotoxicity versus protection.

This study aimed to evaluate the antidotal potency of tenocyclidine (TCP) that probably might protect acetylcholinesterase (AChE) in the case of organophosphate poisoning. TCP was tested alone as a pretreatment or in combination with atropine as a therapy in rats poi- soned with ¼ and ½ of LD50 of soman. Possible genotoxic effects of TCP in white blood cells and brain tissue were also studied. Results were compared with previous findings on the adamantyl tenocyclidine derivative TAMORF. TCP given alone as pretreatment, 5 min be- fore soman, seems to be superior in the protection of cholinesterase (ChE) catalytic activ- ity in the plasma than in brain, especially after administration of the lower dose of soman. Plasma activities of the enzyme after a joint treatment with TCP and soman were signifi - cantly increased at 30 min (P < 0.001) and 24 h (P = 0.0043), as compared to soman alone. TCP and atropine, given as therapy, were more effective than TCP administered alone as a pretreatment. The above therapy significantly increased activities of the enzyme at 30 min (P = 0.046) and 24 h (P < 0.001), as compared to controls treated with ¼ LD50 of soman alone. Using the alkaline comet assay, acceptable genotoxicity of TCP was observed. However, the con- troversial role of TCP in brain protection of soman-poisoned rats should be studied further.