The importance of endogenous catecholamines in the activity of some CNS stimulants

Ten isomers of known central nervous system stimulants were examined for ability to lower chenaoconvulsive threshold. In addition, the involvement of endogenous brain catecholamines in the central activity of these compounds was investigated. The drugs evaluated were d(+) amphetamine,l(−) amphetamine,d(+) pipradrol,l(−) pipradrol,d(−) ephedrine,l(+) ephedrine,d(−)pseudophedrine,l(+)pseudophedrine,d(−) norephedrine, andl(+) norpseudophedrine. All compounds exceptl(−) pipradrol andd(−)pseudoephedrine demonstrated significant effects on chemoconvulsive threshold. The active isomers of amphetamine and ephedrine were shown to possess large indirect components of activity in that central stimulation with these agents was dependent upon small stores of readily available catecholamines. However,d(+) pipradrol and the isomers of norephedrine appeared to have a considerable amount of direct effect on central receptors. No structure-activity relationship for central stimulation was readily apparent.