An Analysis of the Drugs Acting on Cerebral Energy Metabolism

Abstract

Abstract-The behaviour of (a) the redox potential of the lactate/pyruvate system and the changes of the redox potential of the lactate/pyruvate system across the brain; (b) the energy charge potential of the adenylate pool, was studied in the brain of cura rized beagle dogs. The influence of certain drugs (amobarbital, nicergoline, theo phylline, papaverine, bamethan, dipyridamole, bemegride) on these parameters was evaluated under control conditions, during hypoxemia and during post-hypoxiemic recovery. On the whole, the action on energetic metabolism appears to be unrelated to the action believed to be exerted by drugs on cerebral vessels.Some of the basic problems at the cerebral level concern both the ability of drugs to interfere with energy metabolism, and the relationships between energy metabolism and blood flow. Until recently, energy metabolism and blood fluximetry were regarded as being so interdependent that a substance able to increase cerebral blood flow was always regarded as being also useful in the treatment of acute and chronic cerebropathies.Lately, this criterion has been regarded as highly questionable. The present work was planned in order to carry out a critical evaluation of the action of various drugs at the cerebral level by means of experimental methods which in our laboratory have been used for many years in the study of cerebral metabolism. Our investigations were focused on the energy charge of the adenylate pool and on the redox potential of the lactate pyru vate system under control conditions, during hypoxemia and during post-hypoxia recovery.At the same time, the action of various drugs (papaverine, theophylline, nicergoline, di pyridamole, bamethan, bemegride and amobarbital) was evaluated. MATERIALS AND METHODS Animals and anaesthesiaThe experiments were carried out on 84 male beagle dogs aged 240-360 days and weigh ing from 8.7 to 13.2 kg. Before the experiments, the dogs were maintained under the same environmental conditions (22±1°, relative humidity =60±5%) and were fed only a standard diet with water ad libitum.The surgical procedure was performed on animals pre-anaesthetized with urethane (0.4 g/kg i.p.). Electrical activity of the brain was used to determine the degree of anaes thesia (9), which was induced and maintained only during the surgical procedure by chlora lose (20-40 mg/kg i.v.). The anaesthetics affect labile phosphates and the extra and intra cellular brain lactate and pyruvate concentrations (14,21). Therefore the restoration of

Parasympathomimetic Influence of Carbachol on Local Cerebral Blood Flow in the Rabbit by a Direct Vasodilator Action and an Inhibition of the Sympathetic‐mediated Vasoconstriction

“…In comparison, intravenous injection in the rabbit of 2.5 mg/kg of papaverine causes caudate nucleus blood flow to augment by 70% and the tissue Pco2 to diminish by 7.5% Seylaz, Pinard, Dittmar & Birer, 1979). The slightness of the variation of the tissue Pco2 in these 3 cases, and the fact that the action of papaverine has been shown to be purely vascular (Benzi, 1975), provides evidence for an essentially direct vascular action of carbachol in the present experiments. It seems probable therefore that, although the metabolic needs of the brain tissue may be raised with carbachol, the direct vasodilator action of this drug suffices to maintain normal tissue gas levels except when blocked by atropine (0.5 mg/kg i.v.…”