PHARMACOLOGICAL REACTIVITY OF DYSTROPHIC MUSCLE

Abstract

The effects of curarizing drugs, anticholinesterases, and musculotropic substances were studied on the phrenic nerve – diaphragm preparation of the hereditarily dystrophic mouse and of the rat treated with N,N-dimethyl-p-phenylenediamine (PPD), a cytotoxic substance producing dystrophic-like lesions. Both species showed an increased resistance to the neuromuscular blocking activity of d-tubocurarine. Gallamine was also less potent in the dystrophic mouse than in its normal littermate. Both species showed an increased sensitivity to the initial stimulant effect of succinylcholine; on the other hand, the depressant effect of succinylcholine was less intense in PPD-treated rats but unaltered in the dystrophic mouse. The response to neostigmine and physostigmine was decreased in the PPD-treated rat but enhanced in the dystrophic mouse. Musculotropic drugs (chlorpromazine, tetrodotoxin, xanthine derivatives, and veratrine) produced similar effects in normal and dystrophic mice. Two hypotheses are suggested to explain these changes in sensitivity in the dystrophic mouse diaphragm: (a) an increased production of an acetylcholine-like material, and (b) an increase in the number of acetylcholine-sensitive sites on the cell membrane. The changes in drug reactivity of the PPD-treated rat are considered to be due to a functional denervation caused by the cytotoxic properties of PPD.