Protective and restitutive effects of antihypoxic drugs on posthypoxic dopamine release inhibition.
Exposure of rats to hypoxia results in a substantial decrease of dopamine release from striatum slices for several days. Nootropic drugs (piracetam, meclofenoxate hydrochloride, methylglucamine orotate, nicergoline) accelerate the restitution of posthypoxic release inhibition. In contrast, amphetamine is ineffective in this respect. The antihypoxic action of sedatives (diazepam, phenobarbital) prevents the decrease of dopamine release. Comparable results with free radical scavengers (cysteamine hydrochloride, sodium formiate, ouabain), ascorbic acid, natrii calcii edetas, selenium methionine and acetylsalicylic acid which protect dopamine release from hypoxically produced changes agree with and support the hypothesis of hypoxia induced free radical generation followed by phospholipid peroxidation altering particularly neuronal membrane function. On that account, dopamine release from rat striatum slices reflects not only the vulnerability of neuronal membrane function by hypoxia but also the preventive, protective and restitutive effects of antihypoxic drugs of different type and is able to contribute to discriminating drug investigation.
Wustmann
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C
Fischer
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HD
Schmidt
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J
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005609:Free Radicals; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D010889:Piracetam / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D012643:Selenium / Q000494:pharmacology
D000975:Antioxidants; D002614:Chelating Agents; D005609:Free Radicals; D008054:Lipid Peroxides; D011760:Pyrrolidinones; D000661:Amphetamine; D012643:Selenium; D004298:Dopamine; D010889:Piracetam