Age-dependent modification of aspecific cellular effects of the benzodiazepine flunitrazepam

The experiments presented here demonstrate an aspecific effect of the benzodiazepine derivative flunitrazepam (FNZ). It differs in sites and mechanisms of action, both from benzodiazepine (BZ) specific effects on gamma-aminobutyric acid (GABA) blocking transmission via central BZ receptors and from BZ effects mediated by peripheral BZ receptors. The aspecific effect of FNZ can suitably be examined on isolated and identified neurons of the mollusc Lymnaea stagnalis (pond snail). The physiological sites of action are outside the synaptic zone, on the neuron somatic membrane and affect 'intrinsic' properties of membrane, including calcium, calcium-activated potassium and chloride channels. The aspecific FNZ effect exerts an influence on the metabolism of the cell by decreasing the permeability of the calcium channel, diminishing the excitability of the neuron membrane, and hyperpolarizing the cell, thus potentiating the specific effect of FNZ. The senile alterations of the neuron function intensify the aspecific effects of FNZ to such a degree that it must be taken seriously in consideration in anesthesia of elderly patients.