SITE OF ACTION OF MYANESIN (MEPHENESIN, TOLSEROL) IN THE CENTRAL NERVOUS SYSTEM

Abstract

The site of action of myanesin in the central nervous system was studied in cats and monkeys. In therapeutic doses of the drug (10-40 mg./kg. intraven.) the spinal mono- and multisynaptic reflex discharges were unaffected as were the patellar, flexion, and crossed extension reflexes. With increased dosage the multisynaptic reflex discharges were depressed before the mono-synaptic ones. Correspondingly the flexion and crossed extension reflexes were found more susceptible to the drug than the patellar reflexes. In accordance with earlier observations, hyperactive spinal reflexes produced with light chloralose anesthesia or by injn. of strychnine) were promptly reduced to normal with clinical doses of myanesin. The great enhancement of the multineuron discharge following the injn. of strychnine could also be effectively counteracted. Facilitation and inhibition of the knee jerk from stimulation of the brain stem reticular formation were reduced or abolished by myanesin in amts. of 20-30 mg./kg. The stimulus threshold for obtaining these effects was measured before and after the admn. of the drug. In most expts. the 2 systems were about equally depressed, while in some prepns. with very hyperactive reflexes facilitation was somewhat more reduced than inhibition. Similar facilitation and inhibition obtained from the anterior lobe of the cerebellum were reduced with smaller doses of myanesin (10-20 mg./kg.). Cortically induced movements were reduced by doses of 15-35 mg./kg. Spontaneous cortical and subcortical potentials were unaffected by clinical doses of myanesin. The repetitive discharges of the evoked cortical potentials were abolished with smaller doses of the drug than was the primary complex. Cortical after-discharges in chlo-ralosed animals were reduced. It is concluded that the more complex multisynaptic pathways are particularly vulnerable to myanesin. Such pathways are presumably involved in disorders which respond to myanesin, such as spasticity, rigidity, certain involuntary movements, petit mal epilepsy, and possibly certain types of pain.