IT was shown by Green1and Bielschowsky and Green2that injection of the sodium salts of adenosine triphosphate, obtained from Dyckerhoff's “myotoxin”, into a variety of animals resulted in a shock-like syndrome. It was suggested thatthe pyrophosphate group might be responsible for at least some of the described effects.Further investigations on the striated muscle product show that its adenosine triphosphate is present in the form of the magnesium salt. It seemed important to analyse the shock-producing action of adenosine triphosphate by a comparison of the action of related compounds varying in the three components: adenosine -polyphosphoric acid - magnesium.As to the polyphosphoric acid, a detailed study has shown that the injection of Na4PaO,. lOB^O does produce effects similar, in some respects atleast, to those produced by adenosine triphosphate. To study the influence of the adenosine and magnesium in the molecule, solutions of the sodium and magnesium salts of adenosine triphosphate and inosine triphosphate were tested for their lethal and shock-producing potencies in the rat and mouse, and for their depressor activities in the cat. Both salt solutions were prepared from the corresponding barium salts (barium inosine triphosphate from barium adenosine triphosphate by deamination with sodium nitrite), avoiding excess of magnesium, and their concentrations werechecked by estimations of nitrogen and 7 min. phosphorus. A condensed summary of the results of the assays is given in Table 1, and some abstracted data showing a few of the effects in the whole animal are given in Table 2.In both the mouse and rat, the lethal doses of the inosine compounds were significantly higher than those of the corresponding adenosine compounds. Some of the shock-inducing effects of the adenosine triphosphate salts are therefore presumably associated with the presence of the amino group of adenosine. The findings with the sodium salts show that their lethal doses were significantly higher in terms of their pyrophosphate contents than that of sodium pyrophosphate, with the exception of sodium adenosine triphosphate in the mouse. The interpretation of these results is complicated by the fact that the lethal dose of sodium pyrophosphate in the mouse was more than twice that in the rat. In both species the influence of the aminogroup in the sodium adenosine triphos-phate is evident. Nevertheless, the polyphosphoric acid seems to be an important factor since, for example, the lethal dose of muscle adenylic acid is much higher than that of adenosine triphosphate.'The replacement of sodium by magnesium in inosine triphosphate much more than compensates for the loss in activity produced by the substitutionof the NHa group in the adenosine triphosphate by the OH group (inosine triphosphate). This is shown by comparison of the results obtained with magnesium inosine triphosphate and the sodium salts of adenosine triphosphate and inosine triphosphate (Table 1). TABLB l. INTBAPBKITONEAL LETHAL AND INTRAVENOUS DEPRESSOR DOSES OF POLYPHOSPHATES (GROUPS OF 6-12 RATS AND 8-16 MICE).Compound Mouse Eat Cat LD1M (mgm./ PjO, P.,0, LD,M,(mgm./ _ P,p, ^ P,0, Depressor dose: 30 mm. Hg./kilo body wt. (mgm.)bodywt.) (mgm.) P2O, - Mag.aden.triphos. bodywt.) (mgm.) P20, - -Mag. aden.triphos. Magnesium adenosinetriphosphate Magnesium inosine triphosphate Striated muscle product* Sodium adenosine triphosphate Sodium inosine triphosphate 45 14 160 19 1 -4 300 26 1-9 130 38 2-7 240 70, 5-0 50 1670 22 1 -4 340 29 1 -9 100 29 1 -8 120 35 2-2 0-24-00 0-7 0-35Na.P.O, . 10 HSO 120 47 3-4 50 20 1 -3 t * Crude muscle product similar to those from which adenosine triphosphate salts were derived, t No depressor action except in enormous dosage.TABLE 2. GENERAL EFFECTS OF MINIMAL LETHAL DOSES OF ADENOSINE AND INOSINE TRIPHOSPHATE IN THE RAT. (AVERAGE OF 4 RATS.) Compound Hb (Haldane) per cent Hours 0 1 4J Eectal temp. (° C.) Hours 0 1 4i Eespirations per min. Hours 0 1 4J No. surviving at 4J hr.Magnesium adenosine triphosphate Magnesium inosine triphosphate Striated muscle product 96 110 140 91 113 122 102 112 116 37 25 21 36 28 26 36 28 29 94 51 16 94 68 70 103 73 76 1 4 4Na,P,O, 93 119 144 37 28 29 93 60 72 2 It may be assumed, therefore, that the P2O7 group becomes biologically more active, at any rate so far as its shock-producing effects are concerned, when it is combined with both magnesium and either adenylic or inosinic acids. As we have been unable so far to prepare an inorganic magnesium polyphosphate suitable for injection, we do not yet know whether this is due to the influence of the magnesium ion on the polyphosphoric acid group.The magnesium salt of adenosine triphosphate had the greatest potency ofall the substances tested, and using minimal lethal doses a shock-like condition followed the injection much more rapidly (Table 2). It is noteworthy that the quotient P2O7/PaO7-magnesium adenosine triphosphate is the same in both species for magnesium adenosine triphosphate, magnesium inosine triphosphate and the striated muscle product (Table 1), whereas there is a considerable difference between the rat and mouse in the quotients for both sodium adenosine triphosphate and sodium inosine triphosphate. A calculation on the basis that all the adenosine triphosphate in the striated muscle product is present as the magnesium salt accounts fully for its vaso-depressor activity (see Table 1). Its lower shock-producing potency after intraperitoneal injection is probably due to a slower rate of absorption of the magnesium adenosine triphosphate from the crude muscle product. All the data at our disposal make it highly probable that the adenosine triphosphate in striated muscle is present in the formof the magnesium salt. This conception is in good agreement with the results obtained byJSzent-GySrgyi and his collaborat