Central nervous effects of the convulsant protein canatoxin

Abstract

Some pharmacological-toxicological effects of canatoxin, a toxic protein purified from the seeds of Canavalia ensiformis have been studied in mice and rats. The most obvious effect, a lethal tonic convulsion, was generally produced 10-15 min. after intravenous injection of 2-3 mg/kg of the highly purified protein (mol. wt. 88,000). After intraperitoneal, intramuscular or subcutaneous administration the convulsion produced by the same toxin dosis occurred within 24 hours. A spinal transection at the midthoracic level did not abolish the convulsions of the hindlimbs while destruction of the medulla below this level completely blocked the convulsions of the hindlimbs. The convulsions of the head and forelimbs were unaffected by these surgical pretreatments. The toxic protein did neither affect the isolated skeletal muscle nor did it potentiate nerve impulse induced contractions. The convulsive effect of canatoxin was potentiated by reserpine and attenuated by phenobarbital, diazepam, methenesine and also by haloperidol and spiroperidol. The total concentration of brain and spinal cord neurotransmitters seemed to remain unchanged after subconvulsive and convulsive doses of canatoxin. In the conscious rat the toxic protein did not change the blood pressure except for a shortlasting hypertensive response observed immediately before the onset of the convulsions. The heart frequency was lowered at subconvulsive and convulsive doses but no effect was seen on the frequency of the rat isolated right atria exposed to high doses of canatoxin. The body temperature was lowered by a convulsive doses of the toxic protein.(ABSTRACT TRUNCATED AT 250 WORDS)