The effects of Piracetam, Naftidrofuryl and methamphetamine on several parameters of cerebral energy metabolism have been studied. At variance with some reports in the literature neither Piracetam nor Naftidrofuryl affected the cerebral contents of adenine nucleotides and, accordingly, both substances were without effect on the adenylate energy charge. This disagreement is explained by methodological differences. Methamphetamine also had no effect on cerebral adenine nucleotides. Piracetam increased the activity of adenylate kinase (EC 2.7.4.3) in isotonically diluted rat brain homogenates without altering the K(M) of the enzyme for ADP as substrate. It is concluded that although Piracetam has no effect on the cerebral energy metabolism under normal conditions, it may have a beneficial effect under marginal conditions like those met during hypoxia, by virtue of its adenylate kinase stimulating action. It is suggested that this action is responsible for the protective effect of Piracetam against cerebral hypoxia. It may also be related to the enhancement of acquisition under training conditions where cerebral energy metabolism is disturbed. Chemicals/CAS: adenylate kinase, 9013-02-9; methamphetamine, 28297-73-6, 51-57-0, 537-46-2, 7632-10-2; naftidrofuryl, 31329-57-4; piracetam, 7491-74-9; Adenosine Diphosphate, 58-64-0; Adenosine Monophosphate, 61-19-8; Adenosine Triphosphate, 56-65-5; Adenylate Kinase, EC 2.7.4.3; Furans; Methamphetamine, 537-46-2; Nafronyl, 31329-57-4; Piracetam, 7491-74-9; Pyrrolidinones