Interaction of ethanol and thyroxine on mitochondria.
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Biomedical subjects
Publications and source records attributed to R Karler.
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1. The effects of salicylate on oxidative phosphorylation and respiration were investigated in liver and brain mitochondria, and in sonically prepared mitochondrial fragments. 2. Salicylate was shown to uncouple oxidative phosphorylation in mitochondrial fragments, as well as in intact mitochondria. The effects of salicylate on mitochondria and oxidative phosphorylation resemble those produced by dinitrophenol. 3. The quantitative effects of salicylate on respiration in vitro were shown to be complex. The final effect may be the resultant of an interaction of a multiplicity of factors, such as the tissue, the substrate, mitochondrial and extramitochondrial influences, and the direct effect on the respiratory chain itself.
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Comparative studies of the anticonvulsant properties of the cannabinoids and prototype antiepileptic drugs in numerous animal seizure models demonstrate that (1) as an anticonvulsant, cannabidiol (CBD), in contrast to delta 9-tetrahydrocannabinol (THC), is relatively selective in terms of both central nervous system (CNS), depressant and excitatory properties; (2) the potency of cannabidiol, unlike that of phenytoin and phenobarbital, varies greatly with the species; (3) the large potency difference between the cannabinoids and the antiepileptics in the mouse appears to be due to dispositional differences, because brain concentrations of all the drugs are very similar; (4) tolerance to the anticonvulsant properties of cannabidiol is not a prominent feature; in three seizure models, tolerance developed in one, but "reverse tolerance" developed in the other two; and (5) the results of a study of the electrophysiologic mechanisms of action indicate that cannabidiol produces some unique effects and that its spectrum of antiepileptic activity may be different from that of the prototype drugs. The anticonvulsant nature of cannabidiol suggests that it has a therapeutic potential in at least three of the four major types of epilepsy: grand mal, cortical focal, and complex partial seizures.
The effects of the psychoactive cannabinoid delta 9-tetrahydrocannabinol (THC) and the nonpsychoactive cannabinoid cannabidiol (CBD) were investigated comparatively on electrically caused transcallosal cortical evoked responses, electrically induced limbic after discharges, photically evoked cortical afterdischarges, spontaneous cortical focal epileptic potentials, and spinal monosynaptic reflexes. In each system, THC produced central excitation; for example, the drug's responses ranged from enhancement of synaptic transmission to precipitation of frank convulsions. In addition to central nervous system stimulation, THC usually elicited depression; the qualitative character of the effect of the drug was dependent upon the dosage and the test system. In contrast to THC, cannabidiol generated no CNS excitation: it was either depressant or inert in these test systems. The results clearly demonstrate the complexity of the CNS properties of THC and the selectivity of the depressant properties of cannabidiol; moreover, the data illustrate the wide range of neuropharmacologic responses that potentially any cannabinoid can effect.