Effects of carbamazepine on muscle tone in the decerebrate cat

N Hershkowitz, TM Mahany and A Raines

Previous studies, which have demonstrated that carbamazepine (CBZ) possesses direct muscle spindle suppressant activity, suggest that CBZ may have therapeutic value in the treatment of hypertonic disorders characterized by high fusimotor drive. The effects of CBZ on motor tone in the midcollicular decerebrate cat were therefore examined. CBZ, in a concentration-dependent manner, reduced muscle tone, as measured by the force necessary to overcome hyperextension. Significant depression was first observed at a serum concentration of about 25 micrograms/ml, whereas 50% depression occurred at about 40 micrograms/ml. These effects could not be attributed to the hypotensive effect of the drug. CBZ produced little or no effect on spontaneous gamma motoneuron activity recorded in teased ventral roots of segmentally deafferented spinal cords of decerebrate animals; chlorpromazine, however, was effective in suppressing such activity. In the same preparations, CBZ reduced polysynaptic but had little effect on monosynaptic spinal reflexes evoked by dorsal root stimulation. The drug also shortened the duration of the pause in spontaneous gamma motoneuron activity after dorsal root stimulation. Serum concentrations which diminished extensor rigidity in decerebrate cats induced mild to moderate intoxication in intact unanesthetized cats. This was characterized by ataxic gait, sedation and hypotonia. These experiments indicate that CBZ may be of value alone or adjunctively in the reduction of some forms of muscle hypertonicity.

Volume 224, Issue 2, pp. 473-481, 02/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics