Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Aug;94(4):1069–1076. doi: 10.1111/j.1476-5381.1988.tb11624.x

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2-propandiols in the mouse.

F Bowser-Riley 1, S Daniels 1, E B Smith 1
PMCID: PMC1854086  PMID: 3207974

Abstract

1. The effects of a variety of structural isomers of the centrally acting muscle relaxant mephenesin on the high pressure neurological syndrome have been investigated. Threshold pressures for the onset of the behavioural signs, tremors and convulsions, were established. The effects of these compounds on the response to pressure were also compared with their ability to antagonize the convulsive action of strychnine. 2. The dose-response relationships for strychnine and picrotoxin were investigated at fixed pressures. Additionally, the dose-response relationship of strychnine, in the presence of mephenesin, at pressure was investigated. 3. All the isomers of mephenesin protected against the effects of both pressure and strychnine. The relative potency was found to be identical with respect to both. Mephenesin was clearly the most effective; it raised the threshold pressure for tremors by 2.5 times, that for convulsions elicited by pressure by 1.5 and the ED50 for strychnine convulsions by 1.6 times. Strychnine was found to be strictly additive with pressure whereas picrotoxin exhibited gross deviations from additivity. Mephenesin ameliorated the combined effects of pressure and strychnine equally. 4. The marked dependence on structure of the anticonvulsant activity of the mephenesin isomers can be interpreted as evidence that pressure acts not by some general perturbation of the membranes of excitable cells but rather via some specific interaction. The finding that strychnine and pressure are strictly additive supports the idea of specificity and also indicates that they may share a common mechanism in the production of convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1069

Selected References

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

  1. BERGER F. M. Central depressant and anticonvulsant properties of glycerol ethers isomeric with mephenesin. J Pharmacol Exp Ther. 1952 Aug;105(4):450–457. [PubMed] [Google Scholar]
  2. Bennett P. B., Coggin R., McLeod M. Effect of compression rate on use of trimix to ameliorate HPNS in man to 686 m (2250 ft). Undersea Biomed Res. 1982 Dec;9(4):335–351. [PubMed] [Google Scholar]
  3. Bernard C., Ferrary E., Sterkers O. Production of endolymph in the semicircular canal of the frog Rana esculenta. J Physiol. 1986 Feb;371:17–28. doi: 10.1113/jphysiol.1986.sp015959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bichard A. R., Little H. J. Drugs that increase gamma-aminobutyric acid transmission protect against the high pressure neurological syndrome. Br J Pharmacol. 1982 Jul;76(3):447–452. doi: 10.1111/j.1476-5381.1982.tb09238.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bowser-Riley F. Mechanistic studies on the high pressure neurological syndrome. Philos Trans R Soc Lond B Biol Sci. 1984 Jan 7;304(1118):31–41. doi: 10.1098/rstb.1984.0006. [DOI] [PubMed] [Google Scholar]
  6. Curtis D. R., Johnston G. A. Amino acid transmitters in the mammalian central nervous system. Ergeb Physiol. 1974;69(0):97–188. doi: 10.1007/3-540-06498-2_3. [DOI] [PubMed] [Google Scholar]
  7. ECCLES J. C. PRESYNAPTIC INHIBITION IN THE SPINAL CORD. Prog Brain Res. 1964;12:65–91. doi: 10.1016/s0079-6123(08)60618-4. [DOI] [PubMed] [Google Scholar]
  8. Meldrum B., Wardley-Smit B., Halsey M., Rostain J. C. 2-Amino-phosphonoheptanoic acid protects against the high pressure neurological syndrome. Eur J Pharmacol. 1983 Mar 4;87(4):501–502. doi: 10.1016/0014-2999(83)90094-8. [DOI] [PubMed] [Google Scholar]
  9. Miller K. W., Paton W. D., Smith R. A., Smith E. B. The pressure reversal of general anesthesia and the critical volume hypothesis. Mol Pharmacol. 1973 Mar;9(2):131–143. [PubMed] [Google Scholar]
  10. Miller K. W. The nature of the site of general anesthesia. Int Rev Neurobiol. 1985;27:1–61. doi: 10.1016/s0074-7742(08)60555-3. [DOI] [PubMed] [Google Scholar]
  11. Wardley-Smith B., Meldrum B. S. Effect of excitatory amino acid antagonists on the high pressure neurological syndrome in rats. Eur J Pharmacol. 1984 Oct 15;105(3-4):351–354. doi: 10.1016/0014-2999(84)90631-9. [DOI] [PubMed] [Google Scholar]

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

RESOURCES