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Molecular Pharmacology, Vol 11, 379-385, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

The Inhalation Convulsants: a Pharmacodynamic Approach

S. COHEN 1, A. GOLDSCHMID 1, G. SHTACHER 1, S. SREBRENIK 1, and S. GITTER 1

1 Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, and Department of Pharmacy, Kupat-Holim (Health Services), Tel Aviv, Israel

Certain fluorinated ethers, e.g., (CF3CH2)2O, are potent stimulants of the central nervous system. The presence of fluorine in the molecule is not necessarily indicative of this type of activity, since (CF3)2CHOCH3, an isomer, is anesthetic. We have now found that the only reliable experimental parameter that could predict the type of activity in fluorinated ethers is the partial molal volume ([unknown]) in a model solvent. Knowledge of [unknown] allows derivations of the solubility parameter (dgr) and of the partition coefficient that are more dependable than had been hitherto possible. All the inhalation convulsants studied are characterized by low dgr values (6.5-7.5) and incur large rates of expansion in molal volume (4-8%) in benzene solution (dgr = 9.2). Their stimulatory activity could be ascribed to excess free energy (FE) in the biophase large enough to surmount the energetic barrier against the spontaneous influx of Na+, to a preference for accumulating in that phase of a target organ that is compatible with their low dgr, or to a combination of these effects.

Note:
ACKNOWLEDGMENT The authors thank Dr. Z. Elazar for his continued interest and advice.

Submitted on November 25, 1974




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