MOLECULAR STRUCTURE–ACTIVITY RELATIONSHIPS OF COMPOUNDS PROTECTING RATS AGAINST OXYGEN POISONING

Abstract

A number of compounds have been studied to correlate their molecular structure with their efficacy in protecting male Wistar rats against the toxic effects of exposure to oxygen at 75 p.s.i. gauge pressure for 45 minutes. Compounds with a straight chain, 2C to 4C in length, containing one amino and one carboxyl group located at opposite ends of the chain were the most potent protective agents. The presence of an additional amino or carboxyl group or an alkyl side chain in the molecule greatly reduced the protective action as did the removal of either the amino or carboxyl group from the active molecule. The length of the carbon chain within the range 2C to 4C was not critical with respect to the activity of the compound but the position of the amino group appeared to have some bearing on activity, the degree of protection being at a maximum when the amino group was attached to the terminal carbon atom furthest from the carboxyl group. The similarity between the protective action of the amino acids and their depressant action on neurones is commented upon and possible mechanisms involved in oxygen poisoning and protection therefrom by amino acids are discussed.