NEUROMUSCULAR BLOCKING ACTIONS OF NEREISTOXIN AND ITS DERIVATIVES AND ANTAGONISM BY SULFHYDRYL COMPOUNDS

摘要

References(28) Cited-By(7) Chemical and pharmacological studies of a toxin present in Japanese species of a marine annelid, Lumbriconereis heteropoda Marenz, were motivated mainly by the clinical complaints of headache, nausea and respiratory disorder in the fishers using this annelid as a fishing bait. Moreover, it has widely been observed that the feeding of the dead body of this annelid results in the toxic death of carnivorous insects living in seashore. Nitta (1-3) first isolated a toxic principle, nereistoxin from the annelid to characterize partly its chemical and pharmacological properties. The chemical structure of nereistoxin clarified by Okaichi and Hashimoto (4, 5) as N, N-dimethylamino-l, 2-dithiolane was quite different from those of the known toxins. Further, their confirmation of powerful insecticidal activity prompted Hagiwara et al. (6) to synthesize nereistoxin and a number of related compounds. One of the derivatives, 1, 3-bis (carbamoylthio)-2-N, N-dimethyl-aminopropane (Cartap, NTD-2) with low toxicity in the experimental animals and with chemical stability has been successfully used as a potent insecticide against the rice stem borer and many of other agricultural pests. The postsynaptic blocking effect of nereistoxin on the central nervous system in the American coakroach was demonstrated by Sakai (7) as the insecticidal mechanism. Furthermore, he showed that nereistoxin had only slight inhibition of cholinesterase activity in housefly's head (8). On the other hand, we have briefly communicated that nereistoxin produces convulsion and blocking of the neuromuscular transmission in mammals (9). This paper deals with the comparison of the neuromuscular blocking effects between nereistoxin and its derivatives, and with the mechanism of neuromuscular block. The neuromuscular blocking effects of nereistoxin and NTD-2 were found to be antagonized by some of sulfhydryl compounds.