Tetrodotoxin-insensitive central depression by grayanotoxin-III in mice.

Abstract

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.

• Authors: T Ohgaki, H Meguri, K Ogita, Y Yoneda
• Journal: Brain research (Brain Res) Vol. 425 Issue 2 Pg. 364-8 (Nov 10 1987) ISSN: 0006-8993 [Print] Netherlands
• PMID: 2448007 (Publication Type: Journal Article)

Chemical References

• Diterpenes
• Ion Channels
• Tetrodotoxin
• grayanotoxin III

Topics

• Animals
• Brain (drug effects)
• Depression, Chemical
• Diterpenes (pharmacology)
• Electrophysiology
• Ion Channels (physiology)
• Male
• Mice
• Motor Activity (drug effects)
• Muscle Relaxation (drug effects)
• Reflex (drug effects)
• Seizures (chemically induced)
• Tetrodotoxin (pharmacology)