Abstract
Gilman and Barbour 1 have shown that the minimal hypnotic dose (M.H.D.) and the minimal lethal dose (M.L.D.) of magnesium phenobarbital when administered orally to rats are approximately 25 mg./kilo and 275 mg./kilo, respectively. According to the criterion of Issekutz 2 this would suggest a “hypnotic range” of 250 mg./kilo in the rat, or 10 times the M.H.D.
In a series of 232 rats we have found that when sodium phenobarbital and magnesium phenobarbital in freshly made 4% solutions are administered subcutaneously to rats in parallel experiments that there is no essential difference in the toxicity of either salt. The M.L.D. of both salts for rats by the subcutaneous route is close to 215 mg./kilo.
In dogs, the M.L.D. of both the sodium and the magnesium salts of phenobarbital, when administered orally, is in the neighborhood of 115 mg./kilo, and the M.H.D. of each salt is approximately 20 mg./kilo. However, in a series of 28 dogs a comparison was made of the minimal hypnotic response to the intravenous administration of both salts. By the intravenous route we found the M.H.D. to be 15 mg./kilo. No difference in degree of hypnosis was observed in dogs administered less than 30 mg./kilo, but at this dose level magnesium phenobarbital produced a more profound hypnosis than sodium phenobarbital. The dogs administered sodium phenobarbital would nod, or sleep lightly after onset of hypnosis, but were sensitive to noises and would come when called. On the other hand, the dogs administered magnesium phenobarbital would sleep soundly when left alone, and would neither come when called nor respond to noises of the same pitch and intensity as the dogs administered sodium phenobarbital. Further, the excitement state, manifested by struggle, muscular tremors, and rigidity appeared to be somewhat more depressed in the latter than in the former.
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