A STUDY OF ATAXIA AND MUSCLE SPINDLE DEPRESSION PRODUCED IN MAMMALS BY A NEW UNSYMMETRICAL BIS-METHONIUM COMPOUND

¹ Section of Neurophysiology, Institute of Brain Research, University of Tokyo, Tokyo, Japan

The pharmacological property of 2-(3-dimethylaminopropyl)-1,3,3a,4,9,9a-hexahydro-4,9-o-benzeno-2H-benz[f]isoindole dimethiodide (MI-65-S) on motor activities was studied in the cat and in the dog. In the intact animals, the subcutaneous injection of 3 to 5 mg/kg of MI-65-S produced long-lasting locomotor ataxia which resembled that following section of the dorsal roots.

After administration of 3 to 5 mg/kg of MI-65-S subcutaneously to cats, the frequency of discharges in afferent nerves from de-efferented muscle spindles to constant stretch decreased gradually until complete silence was observed. In MI-65-S treated animals, intercollicular decerebration failed to bring about the rigidity which is known to depend on the integrity of muscle spindle activity; however, the alpha type of rigidity produced by anemic decerebration was unaffected by pretreatment.

The electromyographically recorded discharges of the plantar muscle of the dog exhibited an increase in the variability of tonic discharge frequency, as observed following dorsal root section.

The intravenous injection of the decamethonium to MI-65-S treated animals caused characteristic fascicular twitching of extrafusal muscle fibers but no augmentation of the afferent discharges from muscle spindles.

MI-65-S administration failed to affect the discharges from cutaneous touch receptors, spinal monosynaptic and polysynaptic reflex activities, or the electromyogram evoked by muscle nerve stimulation.

On the basis of these results, the locomotor ataxia caused by MI-65-S may reasonably be explained by its preferential blocking of muscle spindle afferent activity.