Actions of sarin on fast-twitch and slow-twitch skeletal muscles of the cat and protective action by anticholinergic drugs

Abstract

1. The organophosphate cholinesterase inhibitor sarin has been studied for its effects on the contraction of fast-twitch (flexor hallucis longus, FHL) and slow-twitch (soleus) muscles in the cat.2. In both muscles lower doses (2.5 to 20 mug intra-arterially) potentiated, and higher doses (20 mug and over) depressed, twitches produced by indirect stimulation. Muscle action potentials became repetitive. There was no simple relationship between degree of inhibition of blood cholinesterase and effect on muscle twitch.3. The effects of the drug on repetitively stimulated muscles were dependent on both dose and frequency of stimulation. Doses of 2.5 to 10 mug increased the degree of fusion of low frequency tetani (10 Hz for FHL, 5 Hz for soleus) but depressed and caused non-maintenance of tetani at high frequencies (150 Hz and above for FHL, 60 Hz and above for soleus). Doses of 20 mug and above depressed and caused non-maintenance of tetani at all frequencies.4. The anticholinergic drug N-ethyl-2-pyrrolidylmethylcyclopentylphenyl glycollate (PMCG) injected intra-arterially protected both muscles from the effects of sarin on twitch but less so from effects on tetani. When given after sarin the drug reversed twitch potentiation and repetitive firing. In contrast, atropine had little effect on the responses to sarin.5. The effects of (+)-tubocurarine were compared with those of PMCG.6. The possible mode of action of PMCG is discussed.