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. 1963 Feb;20(1):106–120. doi: 10.1111/j.1476-5381.1963.tb01302.x

A method for assessing the effects of drugs on the central actions of 5-hydroxytryptamine

S J Corne, R W Pickering, B T Warner
PMCID: PMC1703746  PMID: 14023050

Abstract

Injection of 5-hydroxytryptophan into mice produces a characteristic head-twitch. For a given period of observation this response may be assessed quantitatively either by observing the proportion of mice showing at least one head-twitch (a quantal response) or by counting the number of head-twitches for each mouse (a graded response). A method, based on the quantal response, of investigating the effect of centrally acting compounds on the head-twitch response is described. Evidence is presented that the head-twitches are due to a central action of 5-hydroxytryptamine formed by decarboxylation of 5-hydroxytryptophan. Head-twitches are potentiated by monoamine oxidase inhibitors and by phenytoin. Antagonists tested include an inhibitor of decarboxylase, antagonists of 5-hydroxytryptamine, some antihistamines, major tranquillizers and analgesic and sympathomimetic drugs. Drugs which neither potentiate nor inhibit the response include barbiturates and minor tranquillizers. The method may be valuable in the preliminary examination of compounds likely to have a central action.

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Selected References

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

  1. BLUM B. Head shaking and nystagmus produced by 2,2-diethyl, 1,3-propanediol (prenderol) in the rat. Arch Int Pharmacodyn Ther. 1962 May 1;137:128–136. [PubMed] [Google Scholar]
  2. BOGDANSKI D. F., PLETSCHER A., BRODIE B. B., UNDENFRIEND S. Identification and assay of serotonin in brain. J Pharmacol Exp Ther. 1956 May;117(1):82–88. [PubMed] [Google Scholar]
  3. BONNYCASTLE D. D., BONNYCASTLE M. F., ANDERSON E. G. The effect of a number of central depressant drugs upon brain 5-hydroxytryptamine levels in the rat. J Pharmacol Exp Ther. 1962 Jan;135:17–20. [PubMed] [Google Scholar]
  4. BONNYCASTLE D. D., GIARMAN N. J., PAASONEN M. K. Diphenylhydantoin and brain-levels and 5-hydroxytryptamine. Nature. 1956 Nov 3;178(4540):990–991. doi: 10.1038/178990a0. [DOI] [PubMed] [Google Scholar]
  5. BRODIE B. B., SPECTOR S., SHORE P. A. Interaction of drugs with norepinephrine in the brain. Pharmacol Rev. 1959 Jun;11(2 Pt 2):548–564. [PubMed] [Google Scholar]
  6. GADDUM J. H., VOGT M. Some central actions of 5-hydroxytryptamine and various antagonists. Br J Pharmacol Chemother. 1956 Jun;11(2):175–179. doi: 10.1111/j.1476-5381.1956.tb01049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GEY K. F., PLETSCHER A. Influence of chlorpromazine and chlorprothixene on the cerebral metabolism of 5-hydroxytryptamine, norepinephrine and dopamine. J Pharmacol Exp Ther. 1961 Jul;133:18–24. [PubMed] [Google Scholar]
  8. GOODSELL J. S., TOMAN J. E., EVERETT G. M., RICHARDS R. K. A search for more effective muscle relaxants among the glycerol ethers and dioxolanes. J Pharmacol Exp Ther. 1954 Mar;110(3):251–259. [PubMed] [Google Scholar]
  9. GREIG M. E., WALK R. A., GIBBONS A. J. The effect of three tryptamine derivatives on serotonin metabolism in vitro and in vivo. J Pharmacol Exp Ther. 1959 Oct;127:110–115. [PubMed] [Google Scholar]
  10. GYERMEK L. 5-hydroxytryptamine antagonists. Pharmacol Rev. 1961 Sep;13:399–439. [PubMed] [Google Scholar]
  11. HESS S. M., DOEPFNER W. Behavioral effects and brain amine content in rats. Arch Int Pharmacodyn Ther. 1961 Nov 1;134:89–99. [PubMed] [Google Scholar]
  12. KELLER D. L., UMBREIT W. W. Permanent alteration of behavior in mice by chemical and psychological means. Science. 1956 Oct 19;124(3225):723–724. doi: 10.1126/science.124.3225.723. [DOI] [PubMed] [Google Scholar]
  13. MARSHALL E. F., STIRLING G. S., TAIT A. C., TODRICK A. The effect of iproniazid and imipramine on the blood platelet 5-hydroxytrptamine level in man. Br J Pharmacol Chemother. 1960 Mar;15:35–41. doi: 10.1111/j.1476-5381.1960.tb01207.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. MAXWELL D. R., GRAY W. R., TAYLOR E. M. Relative activity of some inhibitors of mono-amine oxidase in potentiating the action of tryptamine in vitro and in vivo. Br J Pharmacol Chemother. 1961 Dec;17:310–320. doi: 10.1111/j.1476-5381.1961.tb01118.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. OZAKI M., WEISSBACH H., OZAKI A., WITKOP B., UDENFRIEND S. Monoamine oxidase inhibitors and procedures for their evaluation in vivo and in vitro. J Med Pharm Chem. 1960 Dec;2:591–607. doi: 10.1021/jm50013a001. [DOI] [PubMed] [Google Scholar]
  16. RUDY L. H., COSTA E., RINALDI F., HIMWICH H. E. Clinical evaluation of BAS (benzyl analog of serotonin): a tranquilizing drug. J Nerv Ment Dis. 1958 Mar;126(3):284–288. doi: 10.1097/00005053-195803000-00007. [DOI] [PubMed] [Google Scholar]
  17. SCHANBERG S. M., GIARMAN N. J. Drug-induced alterations in the sub-cellular distribution of 5-hydroxytryptamine in rats brain. Biochem Pharmacol. 1962 Mar;11:187–194. doi: 10.1016/0006-2952(62)90073-4. [DOI] [PubMed] [Google Scholar]
  18. SHAW E. N., WOOLLEY D. W. Methylserotonins as potent antimetabolites of serotonin active both in vitro and in vivo. J Pharmacol Exp Ther. 1956 Feb;116(2):164–176. [PubMed] [Google Scholar]
  19. SHAW E., WOOLLEY D. W. Benzyldimethylbufotenin, a powerful antimetabolite of serotonin. Proc Soc Exp Biol Med. 1956 Nov;93(2):217–220. doi: 10.3181/00379727-93-22712. [DOI] [PubMed] [Google Scholar]
  20. SHORE P. A., PLETSCHER A., TOMICH E. G., CARLSSON A., KUNTZMAN R., BRODIE B. B. Role of brain serotonin in reserpine action. Ann N Y Acad Sci. 1957 Mar 14;66(3):609-15; discussion, 615-7. doi: 10.1111/j.1749-6632.1957.tb40751.x. [DOI] [PubMed] [Google Scholar]
  21. SULSER F., WATTS J., BRODIE B. B. On the mechanism of antidepressant action of imipraminelike drugs. Ann N Y Acad Sci. 1962 Jan 13;96:279–288. doi: 10.1111/j.1749-6632.1962.tb50122.x. [DOI] [PubMed] [Google Scholar]
  22. Sherrington C. S. Reflexes elicitable in the cat from pinna vibrissae and jaws. J Physiol. 1917 Dec 6;51(6):404–431. doi: 10.1113/jphysiol.1917.sp001809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. TEDESCHI D. H., TEDESCHI R. E., FELLOWS E. J. Central serotonin antagonist activity of a number of phenothiazines. Arch Int Pharmacodyn Ther. 1961 Jun 1;132:172–179. [PubMed] [Google Scholar]
  24. TEDESCHI D. H., TEDESCHI R. E., FELLOWS E. J. In vivo monoamine oxidase inhibition measured by potentiation of tryptamine convulsions in rats. Proc Soc Exp Biol Med. 1960 Apr;103:680–682. doi: 10.3181/00379727-103-25633. [DOI] [PubMed] [Google Scholar]
  25. TEDESCHI D. H., TEDESCHI R. E., FELLOWS E. J. The effects of tryptamine on the central nervous system, including a pharmacological procedure for the evaluation of iproniazidlike drugs. J Pharmacol Exp Ther. 1959 Jul;126(3):223–232. [PubMed] [Google Scholar]
  26. UDENFRIEND S., WEISSBACH H., BOGDANSKI D. F. Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan. J Biol Chem. 1957 Feb;224(2):803–810. [PubMed] [Google Scholar]
  27. VANE J. R., COLLIER H. O., CORNE S. J., MARLEY E., BRADLEY P. B. Tryptamine receptors in the central nervous system. Nature. 1961 Sep 9;191:1068–1069. doi: 10.1038/1911068a0. [DOI] [PubMed] [Google Scholar]
  28. WITKIN L. B., SPITALETTA P., PLUMMER A. J. Effects of some central depressants on two simple reflexes in the mouse. J Pharmacol Exp Ther. 1959 Aug;126:330–333. [PubMed] [Google Scholar]
  29. ZETLER G., MUELLER W., WARM I. [Jactatio capitis, a pharmacologically-produced motor stereotype in the mouse]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1959;237:247–263. [PubMed] [Google Scholar]

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