Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1971 Jun;42(2):242–253. doi: 10.1111/j.1476-5381.1971.tb07105.x

Pharmacological properties of centrally administered ouabain and their modification by other drugs

N S Doggett, P S J Spencer
PMCID: PMC1667160  PMID: 4326323

Abstract

1. Ouabain given by intracerebroventricular injection to mice in small doses (0·1-0·4 μg) produced a dose related depression of central nervous activity, characterized by a reduction in spontaneous locomotor activity, hypothermia, catalepsy and ptosis, lowered body posture and lack of response to external stimuli. Doses above 0·4 μg were excitatory, convulsant and lethal.

2. The depressant effects could be antagonized by (+)-amphetamine, desmethylimipramine, dibutyryl cyclic 3′5′-adenosine monophosphate and caffeine.

3. The MAO inhibitor nialamide produced only a small antagonism of ouabain, resulting in a greater rate of recovery from the depressant effects of ouabain.

4. The depressant effects were associated with a marked elevation of whole-brain dopamine levels with little change in noradrenaline or 5-hydroxytryptamine.

5. The dopamine-β-hydroxylase inhibitor sodium diethyldithiocarbamate, administered by intracerebroventricular injection, produced effects qualitatively similar to those seen after ouabain.

6. An interference with central transmitter function is postulated as a possible mode of action of intracerebroventricularly injected ouabain.

Full text

PDF

Selected References

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

  1. Abdulla Y. H., Hamadah K. 3',5' cyclic adenosine monophosphate in depression and mania. Lancet. 1970 Feb 21;1(7643):378–381. doi: 10.1016/s0140-6736(70)91514-x. [DOI] [PubMed] [Google Scholar]
  2. BRITTAIN R. T., SPENCER P. S. MEASUREMENT OF BODY TEMPERATURE IN CONSCIOUS SMALL LABORATORY ANIMALS BY MEANS OF AN OESOPHAGEAL THERMOCOUPLE. J Pharm Pharmacol. 1964 Jul;16:497–499. doi: 10.1111/j.2042-7158.1964.tb07501.x. [DOI] [PubMed] [Google Scholar]
  3. BUTCHER R. W., SUTHERLAND E. W. Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine. J Biol Chem. 1962 Apr;237:1244–1250. [PubMed] [Google Scholar]
  4. Barnett A., Taber R. I. The effects of diethyldithiocarbamate and L-dopa on body temperature in mice. J Pharm Pharmacol. 1968 Aug;20(8):600–604. doi: 10.1111/j.2042-7158.1968.tb09820.x. [DOI] [PubMed] [Google Scholar]
  5. Berti F., Shore P. A. A kinetic analysis of drugs that inhibit the adrenergic neuronal membrane amine pump. Biochem Pharmacol. 1967 Nov;16(11):2091–2094. doi: 10.1016/0006-2952(67)90005-6. [DOI] [PubMed] [Google Scholar]
  6. Blackburn K. J., French P. C., Merrills R. J. 5-hydroxytryptamine uptake by rat brain in vitro. Life Sci. 1967 Aug 1;6(15):1653–1663. doi: 10.1016/0024-3205(67)90176-2. [DOI] [PubMed] [Google Scholar]
  7. Bogdanski D. F., Tissari A., Brodie B. B. Role of sodium, potassium, ouabain and reserpine in uptake, storage and metabolism of biogenic amines in synaptosomes. Life Sci. 1968 Apr 1;7(7):419–428. doi: 10.1016/0024-3205(68)90013-1. [DOI] [PubMed] [Google Scholar]
  8. Brittain R. T., Handley S. L. Temperature changes produced by the injection of catecholamines and 5-hydroxytryptamine into the cerebral ventricles of the conscious mouse. J Physiol. 1967 Oct;192(3):805–813. doi: 10.1113/jphysiol.1967.sp008332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Butcher R. W., Sutherland E. W. The effects of the catecholamines, adrenergic blocking agents, prostaglandin E1, and insulin on cyclie AMP levels in the rat epididymal fat pad in vitro. Ann N Y Acad Sci. 1967 Feb 10;139(3):849–859. doi: 10.1111/j.1749-6632.1967.tb41255.x. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. CASHIN C. H., JACKSON H. An apparatus for testing anticonvulsant drugs by electroshock seizures in mice. J Pharm Pharmacol. 1962 Dec;14(Suppl):44T–47T. doi: 10.1111/j.2042-7158.1962.tb10528.x. [DOI] [PubMed] [Google Scholar]
  12. Carlsson A., Lindqvist M., Fuxe K., Hökfelt T. Histochemical amd biochemical effects of diethyldithiocarbamate on tissue catecholamines. J Pharm Pharmacol. 1966 Jan;18(1):60–62. doi: 10.1111/j.2042-7158.1966.tb07773.x. [DOI] [PubMed] [Google Scholar]
  13. Doggett N. S., Spencer P. S., Turner T. A. The pharmacological effects of ouabain administered intracerebrally to conscious mice. Br J Pharmacol. 1970 Sep;40(1):138P–139P. [PMC free article] [PubMed] [Google Scholar]
  14. Ebadi M. S., Carver M. J. The inhibition of transport ATPase by chlorprothixene in brain. Eur J Pharmacol. 1970 Feb;9(2):190–194. doi: 10.1016/0014-2999(70)90299-2. [DOI] [PubMed] [Google Scholar]
  15. Field M., Plotkin G. R., Silen W. Effects of vasopressin, theophylline and cyclic adenosine monophosphate on short-circuit current across isolated rabbit ileal mucosa. Nature. 1968 Feb 3;217(5127):469–471. doi: 10.1038/217469a0. [DOI] [PubMed] [Google Scholar]
  16. GREEFF K., KASPERAT H. [Comparison of the neurotoxic effect of digitalis glycosides and genins following intracerebral and intravenous injection in mice, rats and guinea pigs]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1961;242:76–89. [PubMed] [Google Scholar]
  17. Goldstein M., Ohi Y., Backstrom T. The effect of ouabain on catecholamine biosynthesis in rat brain cortex slices. J Pharmacol Exp Ther. 1970 Jul;174(1):77–82. [PubMed] [Google Scholar]
  18. HALEY T. J., MCCORMICK W. G. Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol Chemother. 1957 Mar;12(1):12–15. doi: 10.1111/j.1476-5381.1957.tb01354.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hermansen K. Evidence for adrenergic mediation of ouabain induced arrhythmias in the guinea pig. Acta Pharmacol Toxicol (Copenh) 1970;28(1):57–65. doi: 10.1111/j.1600-0773.1969.tb00529.x. [DOI] [PubMed] [Google Scholar]
  20. Kleinrok Z., Zebrowska I., Wielosz M. Some central effects of diethyldithiocarbamate administered intraventricularly in rats. Neuropharmacology. 1970 Sep;9(5):451–455. doi: 10.1016/0028-3908(70)90018-3. [DOI] [PubMed] [Google Scholar]
  21. Moore P. F., Iorio L. C., McManus J. M. Relaxation of the guinea-pig tracheal chain preparation by N6,2'-O-dibutyryl 3',5'-cyclic adenosine monophosphate. J Pharm Pharmacol. 1968 May;20(5):368–372. doi: 10.1111/j.2042-7158.1968.tb09761.x. [DOI] [PubMed] [Google Scholar]
  22. Nybäck H., Sedvall G. Influence of drugs on catecholamine metabolism in brain as studied by 14C-tyrosine. Br J Pharmacol. 1968 Sep;34(1):220P–221P. [PMC free article] [PubMed] [Google Scholar]
  23. Persson T., Waldeck B. Effect of protriptyline on the formation of (3H)noradrenaline from (3H)dopa. J Pharm Pharmacol. 1968 Dec;20(12):966–968. doi: 10.1111/j.2042-7158.1968.tb09688.x. [DOI] [PubMed] [Google Scholar]
  24. Seager L. D., Murphree O. D., Monroe B. Behavioral changes in the rat induced by subacute and convulsive doses of digitoxin. Int J Neuropsychiatry. 1965 Aug;1(4):388–390. [PubMed] [Google Scholar]
  25. Spencer P. S., Turner T. A. Blockade of biogenic amine synthesis: its effect on the responses to leptazol and dexamphetamine in rats. Br J Pharmacol. 1969 Sep;37(1):94–103. doi: 10.1111/j.1476-5381.1969.tb09526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tarve U., Brechtlová M. Effects of psychopharmacological agents on brain metabolism. 3. Effects of imipramine and ouabain on the (Na+ plus K+)activated ATPase from brain microsomes and cooperative interactions with the enzyme. J Neurochem. 1967 Mar;14(3):283–290. doi: 10.1111/j.1471-4159.1967.tb09525.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES