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ANTAGONISM OF EVIPAN BY PICROTOXIN, CORAMINE, AND CARDIAZOL
Author(s) -
Das S. C.
Publication year - 1939
Publication title -
quarterly journal of experimental physiology and cognate medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0033-5541
DOI - 10.1113/expphysiol.1939.sp000814
Subject(s) - picrotoxin , respiratory rate , anesthesia , analeptic , respiratory system , stimulation , chemistry , medicine , heart rate , receptor , blood pressure , biochemistry , antagonist
1. The production of a steady state of respiratory depression by continuous intravenous infusion of sodium evipan into rabbits affords a convenient method for measuring the efficiency of analeptic drugs and for comparing their relative activities. 2. Picrotoxin causes an increase in the depth of respiratory movements as well as in the rate, whereas coramine and cardiazol improve the rate of respiration rather than the depth. 3. 0·3 mg. of picrotoxin causes the same increase in amplitude of respiratory stimulation as does 10 mg. of coramine or of cardiazol. Picrotoxin takes about 3‐5 minutes to develop its maximum effect, whilst the action of coramine or of cardiazol reaches its maximum very quickly. 4. When the respiratory depression is severe, coramine often fails to produce a stimulant effect and may even augment the depression. Picrotoxin still produces a stimulant effect in such cases. 5. Picrotoxin is detoxicated at the rate of 1/70 of the amount present per minute, whereas the rate of destruction of coramine is about 1/10 and of cardiazol 1/16 of the amount present per minute. 6. Continuous intravenous infusion of picrotoxin simultaneously with continuous infusion of evipan permits the balancing of evipan and picrotoxin, and it is possible to work up to doses of both drugs, either of which alone would be fatal. There is a linear relation between the doses of evipan and the log. of the doses of picrotoxin which balance each other. 7. Continuous infusion of coramine superimposed on the continuous infusion of evipan at first shows an increase in the respiratory activity, but after some time there is a gradual fall and the final depression may be greater than that produced by evipan alone. This suggests the formation of an intermediary product during coramine metabolism, which has a depressant action and is more stable than coramine. I gratefully acknowledge my indebtedness to Professor A. J. Clark for his advice and help throughout the course of my work. The expenses of this research were defrayed by a grant from the Moray Fund of Edinburgh University.