PHARMACOLOGICAL PROPERTIES OF A BIS-QUATERNARY AMMONIUM SALT OF THE DIBENZO-BICYCLO(2.2.2) OCTANE SERIES, ESPECIALLY ITS DEPRESSANT EFFECT ON THE MUSCLE SPINDLE

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Abstract
The pharmacological properties of 2-(3-dimethyl -aminopropyl)-l,3,3a,4,9,9a-hexahydro-4,9-o-benzeno-2H-benz[f]isoindole dimethiodide (MI-65-S) were investigated. MI-65-S produced a potent and long-lasting ataxia in animals. According to the blocking action of MI-65-S on the autonomic ganglia, a potent fall of blood pressure and relaxation of the nictitating membrane were observed in the cat and dog. The transmission of impulses through the a -endplate was affected only by a large dose and the duration time was very transient. As no considerable changes were observed in the spinal reflex discharges, it may be considered that MI-65-S fails to show a primary action on the central nervous system. The responses of the muscle spindle to stretching was considerably depressed by MI-65-S. The static phase is more susceptible to this compound than the dynamic phase. Following administration of a large dose, the muscle spindle often completely failed to respond even to a maximum stretching. The stimulating action of succinylcholine on the muscle spindle is antagonized by MI-65-S. Some derivatives of MI-65-S show a slow increase in frequency of muscle spindle discharges. From these results, it may be concluded that MI-65-S acts directly on the muscle spindle and produces the decrease in frequency of its discharges, which may be followed by a serious depression in functions of the gamma-system, and consequently, brings about a long-lasting, potent ataxia in the animals.