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. 1977 Feb;59(2):223–229. doi: 10.1111/j.1476-5381.1977.tb07482.x

Mechanism of neurotoxicity of cardiotonic glycosides.

B B Gaitondé, S N Joglekar
PMCID: PMC1667725  PMID: 13903

Abstract

1 In cats intracerebroventricular administration of 5, 10, 20 mug of peruvoside, a cardiac glycoside obtained from the plant, Thevetia neriifolia, and 10 and 20 mug of ouabain, produced marked neurotoxicity. This was dose-related. 2 Prior administration reserpine (2 mg/kg i.m., 500 mug i.c.v.) or tetrabenazine (25 mg/kg i.v., 50 mg/kg i.v. and 2 mg/,g i.c.v.) suppressed the neurotoxicity, but lithium carbonate (100 mg/,g i.p., 2 mg 2.c.v.) and haloperidol (200 mug i.c.v.) were ineffective. 3 Prior administration of 2-bromolysergic acid diethylamide (BOL-148, 200 mug i.c.v.) or p-chlorophenylalanine (PCPA) (400 mg/kg i.p.) suppressed the neurotoxicity induced by peruvoside and ouabain. 4 Perfusion of the lateral ventricles of cats with 10, 20 and 30 mug of peruvoside or ouqbain produced a massive release of 5-hydroxytryptamine (5-HT). This was dose-related. Prior administration PCPA suppressed the release of 5-HT. 5 The results of the findings indicate the involvement of 5-HT in the genesis of neurotoxicity induced by peruvoside or ouabain.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BHATTACHARYA B. K., FELDBERG W. Perfusion of cerebral ventricles: effects of drugs on outflow from the cisterna and the aqueduct. Br J Pharmacol Chemother. 1958 Jun;13(2):156–162. doi: 10.1111/j.1476-5381.1958.tb00211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buterbaugh G. G., Spratt J. L. The possible role of brain monoamines in the acute toxicity of digitoxigenin. J Pharmacol Exp Ther. 1970 Oct;175(1):121–130. [PubMed] [Google Scholar]
  3. FELDBERG W., SHERWOOD S. L. Injections of drugs into the lateral ventricle of the cat. J Physiol. 1954 Jan;123(1):148–167. doi: 10.1113/jphysiol.1954.sp005040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fuxe K., Sjöqvist F. Hypothermic effect of apomorphine in the mouse. J Pharm Pharmacol. 1972 Sep;24(9):702–705. doi: 10.1111/j.2042-7158.1972.tb09093.x. [DOI] [PubMed] [Google Scholar]
  5. GAITONDE B. B., MCCARTHY L. E., BORISON H. L. CENTRAL EMETIC ACTION AND TOXIC EFFECTS OF DIGITALIS IN CATS. J Pharmacol Exp Ther. 1965 Mar;147:409–415. [PubMed] [Google Scholar]
  6. GERSHON S., YUWILER A. Lithium ion: a specific psychopharmacological approach to the treatment of mania. J Neuropsychiatr. 1960 May-Jun;1:229–241. [PubMed] [Google Scholar]
  7. Gaitonde B. B., Joglekar S. N. Mechanism of peruvoside-induced emesis. Neuropharmacology. 1972 May;11(3):427–433. doi: 10.1016/0028-3908(72)90028-7. [DOI] [PubMed] [Google Scholar]
  8. Gaitondé B. B., Joglekar S. N. Role of catecholamines in the central mechanism of emetic response induced by peruvoside and ouabain in cats. Br J Pharmacol. 1975 Jun;54(2):157–162. doi: 10.1111/j.1476-5381.1975.tb06924.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HOLZBAUER M., VOGT M. Depression by reserpine of the noradrenaline concentration in the hypothalamus of the cat. J Neurochem. 1956 May;1(1):8–11. doi: 10.1111/j.1471-4159.1956.tb12048.x. [DOI] [PubMed] [Google Scholar]
  10. MELVILLE K. I., SHISTER H. E. General systemic effects and electrocardiographic changes following injections of digitalis glycosides into the lateral ventricle of the brain. Am Heart J. 1957 Mar;53(3):425–438. doi: 10.1016/0002-8703(57)90177-1. [DOI] [PubMed] [Google Scholar]
  11. MUSCHOLL E., VOGT M. The action of reserpine on the peripheral sympathetic system. J Physiol. 1958 Apr 3;141(1):132–155. doi: 10.1113/jphysiol.1958.sp005961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. PLETSCHER A., SHORE P. A., BRODIE B. B. Serotonin release as a possible mechanism of reserpine action. Science. 1955 Aug 26;122(3165):374–375. doi: 10.1126/science.122.3165.374. [DOI] [PubMed] [Google Scholar]
  13. SCHOU M. Lithium in psychiatric therapy. Stock-taking after ten years. Psychopharmacologia. 1959;1:65–78. doi: 10.1007/BF00408113. [DOI] [PubMed] [Google Scholar]
  14. SHORE P. A., SILVER S. L., BRODIE B. B. Interaction of serotonin and lysergic acid diethylamide (LSD) in the central nervous system. Experientia. 1955 Jul 15;11(7):272–273. doi: 10.1007/BF02161252. [DOI] [PubMed] [Google Scholar]
  15. VANE J. R. A sensitive method for the assay of 5-hydroxytryptamine. Br J Pharmacol Chemother. 1957 Sep;12(3):344–349. doi: 10.1111/j.1476-5381.1957.tb00146.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. VOGT M. The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J Physiol. 1954 Mar 29;123(3):451–481. doi: 10.1113/jphysiol.1954.sp005064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Vogt M. Functional aspects of the role of catecholamines in the central nervous system. Br Med Bull. 1973 May;29(2):168–172. doi: 10.1093/oxfordjournals.bmb.a070989. [DOI] [PubMed] [Google Scholar]

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