Stimulants cerebral blood flow, metabolism

In the face of the failure of rational approaches in the treatment of AzD it is perhaps not surprising that there have been many less rational ones. These include the use of vasodilators and nootropics. The former, such as hydergine, a mixture of ergot alkaloids, are intended to increase cerebral blood flow and neuronal metabolism despite some reduction in blood pressure, while the latter, like piracetam, are metabolic stimulants that increase cerebral metabolism and ATP production. Neither are of proven value in AzD. 

During phase I, each seizure causes a sharp increase in autonomic activity with increases in epinephrine, norepinephrine, and steroid plasma concentrations, resulting in hypertension, tachycardia, hyperglycemia, hyperthermia, sweating, and salivation. Cerebral blood flow is also increased to preserve the oxygen supply to the brain during this period of high metabolic demand. Increases in sympathetic and parasympathetic stimulation with muscle hypoxia can lead to ventricular arrhythmias, severe acidosis, and rhabdomyolysis. These, in turn, could lead to hypotension, shock, hyperkalemia, and acute tubular necrosis. 

Fox, P. T. and Raichle, M. E. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc. Natl Acad. Sci. U.S.A. 83 1140-1144,1986. 

H. R. Heekeren, M. Kohl, H. Obrig, R. Wenzel, W. v. Pannwitz, S. Matcher, U. Dirnagl, C. E. Cooper, and A. Villranger. Noninvasive assessment of changes in cytochrom-c-oxidase oxidation in human subjects during visual stimulation. Journal of Cerebral Blood Flow and Metabolism, 19 592-603, 1999. 

In addition to autonomic effects, areca produces mental stimulation, increases cerebral blood flow and glucose metabolism, and creates electrophysiological activation as seen on the EEG. 

Neuroimaging techniques assessing cerebral blood flow (CBF] and cerebral metabolic rate provide powerful windows onto the effects of ECT. Nobler et al. [1994] assessed cortical CBE using the planar xenon-133 inhalation technique in 54 patients. The patients were studied just before and 50 minutes after the sixth ECT treatment. At this acute time point, unilateral ECT led to postictal reductions of CBF in the stimulated hemisphere, whereas bilateral ECT led to symmetric anterior frontal CBE reductions. Regardless of electrode placement and stimulus intensity, patients who went on to respond to a course of ECT manifested anterior frontal CBE reductions in this acute postictal period, whereas nonresponders failed to show CBF reductions. Such frontal CBF reductions may reflect functional neural inhibition and may index anticonvulsant properties of ECT. A predictive discriminant function analysis revealed that the CBF changes were sufficiently robust to correctly classify both responders (68% accuracy] and nonresponders (85% accuracy]. More powerful measures of CBF and/or cerebral metabolic rate, as can be obtained with positron-emission tomography, may provide even more sensitive markers of optimal ECT administration. 

A majority of these agents have been developed initially as peripheral vasodilators which have then been tested for their ability to increase cerebral blood flow on quite empirical grounds. The second group contains those which stimulate neuronal metabolism, the resultant increase in local perivascular CO2 production consequently causing vasodilatation. The former group will be referred to as Vasotropic dilators and the latter as Cerebrometabolic stimulants. ... 

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