Studies were conducted on the actions of counterirritants on muscle contractile mechanisms and nerve conduction in both isolated and intact preparations. Neuromuscular transmission was noncompetitively blocked with menthol and methyl salicylate (MS) and recovered to the control level after they were washed out. Contractions of the isolated frog rectus in response to ACh and electrical stimulation were antagonized with menthol, MS, and camphor; and the action of nonylic vanillyl amide (NVA) became irreversible at high concentration. Menthol and MS produced muscle contraction per se at high concentration and enhanced the caffeine elicited contractile activity. The enhancement was also seen with camphor. The amplitude of the action potential was reduced with menthol, camphor, and MS in a dose and time dependent manner in the isolated frog sciatic nerve. This action was also confirmed in the intraaxonal recordings and was more easily influenced in the small fibres than the large ones. Conduction of primary afferents from muscle and motoneuron was weakly restrained 30 min after the external application of plasters which contained menthol or camphor on the hair-removed skin of cat's hind limb. The refractory period was also apt to be prolonged, and there was an obvious disappearence of group II and III inhibition after the external application of menthol plasters without any effects on group Ia and group Ib inhibition. Concentrations of menthol, camphor, and MS in the muscle that were percutaneously absorbed after the external application of plasters containing these drugs in usual dosage were 10 ?? 30, (ca.) 5, and 5 ?? 10μg/g tissue, respectively. These findings suggest that menthol, camphor, and MS have conductive anesthetic activities mainly being attributable to a suppression of Na
+ activation, and they cause an inhibition of nerve conduction, neuromuscular transmission and excitation contraction coupling, and stabilization on the membrane of the ACh receptor. When plasters containing menthol or camphor, in high dose, are externally applied on the skin, weak conductive anesthetic actions are thought to appear which result from the percutaneously absorbed drugs. Counterirritants, in high dose, cause an enhancement on caffeine elicited contraction and muscle contraction per se.
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