Abstract
1. The fatal intramuscular dose of phyostigmin salicylate for the cat is 1 mgm. per kilogram; when this amount is administered in fractions the action persists about three or four hours.
2. Evidence is presented that the potential capacity of the body to eliminate physostigmin is greater than the duration of action of the drug indicates. If the combination of physostigmin with specific, and, perhaps non-specific, structures is prevented, the cat is capable of ridding itself of about 15 to 20 times the amounts eliminated under normal conditions within similar periods.
3. The antagonism of atropin to physostigmin in the rabbit, described by Fraser, occurs also in the cat. The administration of atropin in the amounts stated prevents death after the administration of physostigmin equal to about 15 times the average fatal intramuscular or intravenous dose; the latter being administered slowly.
4. There is a quantitative ratio between the antagonistic doses of physostigmin and atropin, as described by Fraser. This ratio is not the same apparently in the various structures of the body. The antagonism is complete with relatively small doses of atropin in the secretory system, in the smooth muscles of the intestines, and at the seat of the clonic convulsions (probably, in the medulla). The antagonism is limited and incomplete at the myoneural junction (probably, the seat of the fibrillary twitchings), and in the respiratory center.
5. A dose of atropin which is comparable with a large therapeutic dose in man prevents death following the administration of an otherwise minimal fatal dose of physostigmin in the cat.
6. Man is capable of eliminating at least 1 mgm. of physostigmin every hour and a half to two hours.
7. The antagonism of atropin to physostigmin is effective in man when therapeutic doses of the drug are administered.
8. The therapeutic doses of physostigmin are incompatible with those of atropin and hyoscin.
9. Observations on animals and man indicate that large therapeutic doses of atropin or hyoscin are capable of preventing death from physostigmin.
Footnotes
- Received September 18, 1925.
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