Prediction of convulsant activity of gases and vapors.

European journal of medicinal chemistry (2008-07-08)
Michael H Abraham, William E Acree
ABSTRACT

The convulsant activity of 48 compounds studied by Eger et al. has been analyzed using an Abraham solvation equation. Four compounds identified by Eger et al. as more potent than expected were similarly identified, and for the remaining 44 compounds, the equation had R(2)=0.978 and a standard deviation of 0.17 log units. The structural features of compounds that lead to convulsant activity or to anesthetic activity are uncovered, and used to explain which compounds will act as convulsants and which compounds will act as anesthetics. The present equation for convulsant activity and our previous equation for inhalation anesthetic activity can be used to predict convulsant pressure and anesthetic pressure. For all 48 compounds, the predicted convulsant pressure is less than the predicted anesthetic pressure, in agreement with experiment. Although convulsants tend to have a small hydrogen bond acidity, this is not the only factor that influences the effect. The difference between the compound pressure needed to produce convulsions and that needed to produce anesthesia is quite small for many of the 48 compounds, and so minor structural features can be significant. These structural features are incorporated into our equations that successfully predict convulsant/anesthetic effects for the 48 compounds.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cyclohexane, anhydrous, 99.5%
Sigma-Aldrich
Pentane, anhydrous, ≥99%
Sigma-Aldrich
Cyclohexane, ACS reagent, ≥99%
Sigma-Aldrich
Octane, anhydrous, ≥99%
Sigma-Aldrich
Pentane, suitable for HPLC, ≥99.0%
Sigma-Aldrich
Cyclohexane, suitable for HPLC, ≥99.7%
Sigma-Aldrich
Pentane, reagent grade, 98%
Sigma-Aldrich
Octane, reagent grade, 98%
Sigma-Aldrich
Cyclohexane, puriss. p.a., ACS reagent, ≥99.5% (GC)
Sigma-Aldrich
Nonane, ReagentPlus®, 99%
Sigma-Aldrich
Cyclohexane, Laboratory Reagent, ≥99.8%
Sigma-Aldrich
Pentane, ≥99% (GC)
Supelco
Octane, analytical standard
Sigma-Aldrich
Nonane, anhydrous, ≥99%
Sigma-Aldrich
Octane, puriss. p.a., ≥99.0% (GC)
Sigma-Aldrich
Cyclooctane, ≥99%
Supelco
Nonane, analytical standard
Supelco
Pentane, analytical standard
Sigma-Aldrich
1,3,5-tris(trifluoromethyl)benzene, 97%
Sigma-Aldrich
Octafluorotoluene, 98%
Sigma-Aldrich
Cyclohexane, ACS reagent, ≥99%
Sigma-Aldrich
Pentane, puriss. p.a., ≥99.0% (GC)
Supelco
Nonane, analytical standard
Sigma-Aldrich
Pentane, spectrophotometric grade, ≥99%
Sigma-Aldrich
Cycloheptane, 98%
Sigma-Aldrich
Octane, electronic grade, ≥99.999% metals basis, ≥99% (CP)
Supelco
1,4-Difluorobenzene, analytical standard
Supelco
1,1,2-Trichlorotrifluoroethane, HPLC grade, ≥99.9%