Author(s): Eisenach JC, Hood DD, Curry R
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Abstract Intrathecal (i.t.) neostigmine produces analgesia in humans with acute experimental, postoperative, and chronic pain. The sole manufacturer of the preservative-free neostigmine solution used in the initial clinical studies no longer markets this preparation. Although solutions containing preservatives are generally avoided for i.t. injection, methyl- and propylparabens have not been demonstrated to be toxic. After preclinical toxicity screening in animals and Food and Drug Administration approval, 12 volunteers received i.t. neostigmine 10, 30, or 100 micrograms, containing these preservatives and glucose. This preparation produced dose-dependent analgesia, nausea, weakness, and sedation similar to the preservative-free preparation. I.t. neostigmine increased acetylcholine but not norepinephrine concentrations in cerebrospinal fluid. Although nitric oxide synthesis has been implicated in analgesia from i.t. neostigmine injection in animals, cerebrospinal fluid concentrations of nitrite as a measure of nitric oxide were not increased by i.t. neostigmine in these volunteers. These data support the investigational application of i.t. neostigmine containing methyl- and propylparabens in the concentrations studied. IMPLICATIONS: Because intrathecal injection of neostigmine may be a useful analgesic, we performed a Phase I tolerability and safety study of the commercially available neostigmine formulation in human volunteers and found no evidence of toxicity. These data are important to the clinical use of this new therapy.
This article was published in Anesth Analg
and referenced in Journal of Anesthesia & Clinical Research