New aspects in the pharmacology of kindling implications for mechanism of of action in kindling.

Kindling is a long-lasting, transsynaptic, pathway-specific plastic change in brain function. It has been proposed as a model of neural plasticity, learning and memory, as well as a model of epilepsy. To elucidate the action of substances characterized by their ability to improve learning and memory and to have an activatory, protective and function restoring effect on nerve cells in distress, the effects of nootropic drugs and of antioxidative acting substances on the development of kindling and the seizure behavior in the kindled state were investigated. Nootropic drugs suppress the development of pentetrazol (PTZ)- and amygdala-kindling and possess anticonvulsive potency preferentially in kindled rats. In comparison to amygdala-kindling the substances were found to be more effective against PTZ-kindled seizures. Chemically different antioxidants in doses known to scavenge free radicals suppress markedly the development of kindling and possess anticonvulsant potency in chemically and electrically kindled rats. The results provide arguments in favor of functional alterations of transmission relevant membrane processes with structural and functional reorganization of membrane constituents and lead to the assumption that the changes mainly in part rest on a selective and focal involvement of free radicals. It is proposed that enhanced calcium entry into neurons and consequent biochemical alterations connected with a focal increase in free radicals is part of the mechanisms underlying kindling phenomenon.