Comparative electrophysiological investigations on oxiracetam and piracetam

Acute effects of the two psychogeriatric agents, oxiracetam (ISF 2522) and piracetam, were studied in rat brain tissue in vivo and in vitro. In vivo, both compounds elicited a moderate activation of locus coeruleus neuronal discharge rate with doses of 1,000 mg/kg ip. Neither of the compounds however affected spontaneous firing rates of neurons of the medial septal nucleus in vivo if administered intravenously. In the hippocampal slice preparation, the two compounds elicited weak but opposite effects on extracellularly recorded field potentials if administered in high concentrations. Whereas oxiracetam elicited a moderate depressant effect on pyramidal cell excitability, piracetam increased it in a reversible fashion. Piracetam had no effect on the excitatory postsynaptic potential (epsp) evoked by stimulation of the Schaffer commissural fiber pathway but oxiracetam reversibly attenuated it at concentrations of 100 microM to 1 mM. In intracellular recordings from CA1 pyramidal neurons in vitro, piracetam had no effect on resting membrane potential, conductance or afterhyperpolarizations. Oxiracetam, however, slightly hyperpolarized six out of twelve CA1 neurons. Membrane conductance was not affected. In conclusion, electrophysiological studies with the psychogeriatrics oxiracetam and piracetam revealed that the drugs exert weak effects on rat brain tissue in acute experiments, and demonstrated that the two compounds differ in their pharmacological profile.