Tetrodotoxin-insensitive central depression by grayanotoxin-III in mice.
The effect of systemic administration of grayanotoxin (GTX)-III, a constituent in leaves of Pieris japonica D. Don with an ability to activate the voltage-sensitive sodium channels in excitable tissues, on general behaviors of animals was studied using Std-ddy mice. Intraperitoneal administration of the toxin (0.1-0.25 mg/kg b. wt.) resulted in a dose-dependent manner in a significant and reversible muscle relaxation, and a profound and long lasting (greater than or equal to 60 min) depression of locomotor activity. Pretreatment with GTX-III caused a profound potentiation of the duration of loss of righting reflex by pentobarbital with a concomitant delay of the onset of convulsive seizures by various convulsants such as strychnine, picrotoxin and pentetrazol. Neither tetrodotoxin (1-5 micrograms/kg, i.p.) nor Ro15-1788 (1-5 mg/kg, i.p.) prevented the GTX-III-induced suppression of locomotor activity. These results suggest that GTX-III may elicit a central depressant action in mice through a molecular mechanism other than activation of the voltage-sensitive sodium channels in the brain.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003864:Depression, Chemical; D004224:Diterpenes / Q000494:pharmacology*; D004594:Electrophysiology; D007473:Ion Channels / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced; D013779:Tetrodotoxin / Q000494:pharmacology*
D004224:Diterpenes; D007473:Ion Channels; D013779:Tetrodotoxin; C020751:grayanotoxin III