The Ferguson principle and an analysis of biological activity of gases and vapors.
The Ferguson principle, that Pnar/PO (Pnar is the partial pressure of a series of compounds giving rise to a particular effect on a given system by a physical mechanism, and PO is the saturated vapor pressure of the liquid narcotic) is constant for a series of nonreactive narcotics or toxicants in a given system, is examined and shown to have no thermodynamic basis, contrary to the position of Brink and Posternak. Conditions under which Pnar/PO might be expected to be roughly constant, as an empirical observation, are set out and it is shown that such an observation is consistent with a receptor area in which the liquid narcotic solubilities are roughly constant. An interpretation of relationships between agonist descriptors and biological effects is carried out with three simple biological models. It is shown that the biological potency of nonreactive gases and vapors can be controlled either by an equilibrium between the agonist in the gas phase and the agonist in a receptor or by an equilibrium between the agonist in the gas phase and the agonist in a receptor phase. It is further shown that with the solvation equation of Abraham, solvents can be chosen that mimic the chemical properties of the receptor or receptor phase. For the example of upper respiratory tract irritation of male Swiss OF1 mice, such solvents include N-formylmorpholine, a trialkylphosphate, and wet octanol, but not water itself.
Abraham
M H
MH
Department of Chemistry, University College London, U.K.
Nielsen
G D
GD
Alarie
Y
Y
D002627:Chemistry, Physical / Q000379:methods*; D005740:Gases / Q000737:chemistry* / Q000633:toxicity; D007222:Inert Gas Narcosis / Q000209:etiology; D007700:Kinetics; D008432:Mathematical Computing; D010313:Partial Pressure; D012995:Solubility; D012996:Solutions; D013816:Thermodynamics
D005740:Gases; D012996:Solutions