Effect of Procaine Hydrochloride on Cyanide Intoxication and Its Effect on Neuronal Calcium in Mice

Abstract

Cyanide intoxication in mice can be antagonized by the local anesthetic, procaine HCl, either alone or in combination with sodium nitrite and/or sodium thiosulfate. Antitoxic potency, derived from LD50 values, was compared in groups of mice pretreated with sodium nitrite (43.9 mg/kg ip), sodium thiosulfate (1 g/kg ip), and procaine HCl (37.0 mg/kg ip) either alone or in various combinations. The results of present study indicated that procaine HCl provides a significant protection against the lethal effects of potassium cyanide. Dose–response studies revealed procaine hydrochloride pretreated 3 min before KCN, at doses of 18.48–73.9 mg/kg, produced significant elevation of KCN LD50, moreover it has a good dose–effect relationship, but its antidotal effect was weaker than sodium nitrite or sodium thiosulfate when they were administered alone. The protective effect of sodium nitrite and sodium thiosulfate was enhanced with procaine HCl. When procaine was administered in combination both with sodium nitrite and sodium thiosulfate, its protective effects were further enhanced. Its antitoxic potency is 6.22. The effects of procaine on antagonizing the cyanide-induced whole-brain total calcium increase were also studied. KCN (7 mg/kg ip) significantly increased whole-brain total calcium level from 28.37 ± 0.75 to 48.05 ± 1.06 mg/g dry wt within 30 min, which can be prevented by procaine pretreated 15 min before KCN. One of the possible mechanism of procaine on antagonizing cyanide toxicity seems, at least, related to its effect on inhibiting the cyanide-induced neuronal calcium increase and maintaining the homeostasis of neuronal calcium.