ACTION OF INTRATHECALLY INJECTED PROSTIGMINE, ACETYLCHOLINE, AND ESERINE ON THE CENTRAL NERVOUS SYSTEM IN MAN

1. Prostigmine was injected in doses of 0·1‐1·5 mg. intrathecally 73 times in 37 patients (with evidence of pyramidal tract involvement) and in 3 subjects with normal central nervous system. In all cases it produced depression of muscle tone and reflexes by a direct action on the spinal cord. The distal part of the cord was involved first and the depression gradually ascended to involve the centres controlling the arms. The face was involved rarely. Changes in blood‐pressure, pulse‐rate and respiration were small and irregular. Nausea, vomiting, and drowsiness commonly occurred when large doses were employed. Voluntary movement was impaired. Bladder emptying was temporarily abolished. No changes in sensation were ever noted. Observations were made in patients with spinal block. Injection of prostigmine intrathecally below the level of the block produced depression of the spinal cord limited strictly to the cord below the level of the block. No general disturbances such as nausea or drowsiness developed. In such cases flexor tone, flexor spasms, and flexor reflexes were abolished at the same rate and to the same degree as extensor reflexes. All the above actions of prostigmine are unaffected by subcutaneous injections of atropine. They contrast markedly with the results of injection of prostigmine intramuscularly or intravenously. 2. Intrathecally injected acetylcholine in doses of 2‐500 mg. had no effects on the spinal cord or elsewhere. 10 mg. of acetylcholine injected together with 0·1 mg. of prostigmine produced effects on the spinal cord in every way similar to those of larger doses of prostigmine. 3. Eserine sulphate in doses of 0‐25‐1 mg. injected intrathecally produces an initial transient depression of spinal reflexes followed by a rapid return to a level exceeding that noted prior to the injection. Experiments in a case of spinal block show that both the initial depression and the secondary excitation are due to a direct action on the spinal cord—the effects being limited to the cord region distal to the block. In this case too the excitatory phase of the response was particularly striking, involving both flexor and extensor reflexes. Unlike prostigmine, eserine produces striking sensory changes including facilitation of sensory transmission. Suggestions are made to explain the difference in central action of prostigmine and eserine. This work was interrupted by the outbreak of the War. I gratefully express my thanks to Professor Francis Fraser in whose department the research was carried out, to Professor Samson Wright for his help in the preparation of the paper, and to the Medical Officer of Health, London County Council, for permission to include the notes on the patients.