Abstract

The 24-hr, ip LD50 of triethylene glycol dinitrate (TEGDN) in rats is 995 (1063-932) mg/kg. The ip LD50 of TEGDN in rats anesthetized with pentobarbital is only 321 (605-170) mg/kg. Significant increases in pentobarbital sleep times were observed in rats pretreated with 50 mg of TEGDN/kg ip. Higher doses of TEGDN ameliorated Metrazol toxicity and increased zoxazolamine paralysis times. The peripheral nervous system toxicity of TEGDN was compared to that of decamethonium (C 10). Both compounds caused severe tremors and clonic convulsions in vivo, and in vitro both selectively blocked nerve stimulated contractions of the cholinergic rat phrenic nerve diaphragm (PND) preparation, with C 10 being 60 times more potent in this respect than was TEGDN. When TEGDN and C 10 were applied to PND preparations in combination, the inhibition of the force of contraction occurred more rapidly and was greater than that expected from either compound applied alone. It appears that TEGDN and C 10 act at the same site in vivo in the peripheral nervous system to block cholinergic transmission.

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