Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1980 Mar;68(3):525–532. doi: 10.1111/j.1476-5381.1980.tb14568.x

Antagonism of 5-hydroxytryptamine receptors by quipazine.

M J Lansdown, H L Nash, P R Preston, D I Wallis, R G Williams
PMCID: PMC2044206  PMID: 7052342

Abstract

1 The antagonist actions of quipazine on 5-hydroxytryptamine (5-HT) receptors have been investigated in the rabbit isolated superior cervical ganglion and on the rat isolated spinal cord and stomach strip. 2 Changes in membrane potential induced by 5-HT or by the nicotinic agonist, 1,1-dimethyl-4-phenyl piperazinium (DMPP), were measured in the ganglion by the sucrose-gap technique. At ganglionic receptors, quipazine had little or no agonist activity, but greatly depressed depolarizations evoked by 5-HT but not depolarizations evoked by DMPP or trimethylammonium (TMA). Injections into the superfusion stream to the ganglion of 2 to 5 mumol quipazine in a small volume of Krebs solution prevented all subsequent responses to 5-HT. Superfusion of the ganglion with quipazine at a concentration of 1 microM produced complete blockade of responses to 5-HT in 3 of 6 ganglia and reduced responses by over 90% in 2 others; responses to DMPP were potentiated in amplitude and duration. Superfusion at a concentration of 0.1 microM depressed responses to 5-HT by 75% on average. The threshold concentration for the blocking action was around 0.01 microM, which depressed responses by 42% on average in 6 experiments (range 0 to 75%). 3 5-HT (1 microM or 100 microM) depressed the amplitude of the dorsal root potentials recorded from the isolated, hemisected cord of the neonate rat by 27 +/- 5% (mean +/- s.e. mean, n = 14) and by 45 +/- 6% (n = 14), respectively. In the presence of quipazine (0.01 microM), 5-HT (1 microM or 100 microM) depressed the amplitude by 6 +/- 2% (n = 15) and by 3 +/- 1% (n = 7), respectively. 4 Concentration-response curves of the contractions induced by 5-HT in the fundus of the rat stomach were obtained in the absence and presence of quipazine. Quipazine (1 microM) shifted the concentration-response curve to the right and depressed the maximum, suggesting a non-competitive mode of antagonism. pI50 values were calculated in order to assess the antagonist activity of quipazine at rat fundus 5-HT receptors; the mean pI50 was 6.91 +/- 0.2 (n = 6). 5 It is concluded that quipazine may be an effective antagonist at 5-HT receptors in various tissues.

Full text

PDF
525

Selected References

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

  1. ECCLES J. C., ECCLES R. M., MAGNI F. Central inhibitory action attributable to presynaptic depolarization produced by muscle afferent volleys. J Physiol. 1961 Nov;159:147–166. doi: 10.1113/jphysiol.1961.sp006798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Evans R. H., Francis A. A., Watkins J. C. Selective antagonism by Mg2+ of amino acid-induced depolarization of spinal neurones. Experientia. 1977 Apr 15;33(4):489–491. doi: 10.1007/BF01922227. [DOI] [PubMed] [Google Scholar]
  3. Fozard J. R., Mobarok ALI A. T. Blockade of neuronal tryptamine receptors by metoclopramide. Eur J Pharmacol. 1978 May 1;49(1):109–112. doi: 10.1016/0014-2999(78)90228-5. [DOI] [PubMed] [Google Scholar]
  4. GADDUM J. H., PICARELLI Z. P. Two kinds of tryptamine receptor. Br J Pharmacol Chemother. 1957 Sep;12(3):323–328. doi: 10.1111/j.1476-5381.1957.tb00142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Green A. R., Youdim M. B., Grahame-Smith D. G. Quipazine: its effects on rat brain 5-hydroxytryptamine metabolism, monoamine oxidase activity and behaviour. Neuropharmacology. 1976 Mar;15(3):173–179. doi: 10.1016/0028-3908(76)90026-5. [DOI] [PubMed] [Google Scholar]
  6. Görlitz B. D., Frey H. H. Letter: Comparison of the blocking effects of antagonists of adrenaline and 5-hydroxytryptamine on their mutual receptors. J Pharm Pharmacol. 1973 Aug;25(8):651–653. doi: 10.1111/j.2042-7158.1973.tb10654.x. [DOI] [PubMed] [Google Scholar]
  7. Lansdown M. R., Nash H. L., Preston P. R., Wallis D. I. Blockade of 5-hydroxytryptamine (5-HT) receptors by quipazine [proceedings]. Br J Pharmacol. 1979 May;66(1):80P–81P. [PMC free article] [PubMed] [Google Scholar]
  8. Lees G. M., Wallis D. I. Hyperpolarization of rabbit superior cervical ganglion cells due to activity of an electrogenic sodium pump. Br J Pharmacol. 1974 Jan;50(1):79–93. doi: 10.1111/j.1476-5381.1974.tb09595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Proudfit H. K., Anderson E. G. New long latency bulbospinal evoked potentials blocked by serotonin antagonists. Brain Res. 1974 Jan 18;65(3):542–546. doi: 10.1016/0006-8993(74)90246-7. [DOI] [PubMed] [Google Scholar]
  10. Rack P. M. The behaviour of a mammalian muscle during sinusoidal stretching. J Physiol. 1966 Mar;183(1):1–14. doi: 10.1113/jphysiol.1966.sp007848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rodríguez R., Rojas-Ramírez J. A., Drucker-Colín R. R. Serotonin-like actions of quipazine on the central nervous system. Eur J Pharmacol. 1973 Nov;24(2):164–171. doi: 10.1016/0014-2999(73)90067-8. [DOI] [PubMed] [Google Scholar]
  12. Réthelyi M., Szentágothai J. The large synaptic complexes of the substantia gelatinosa. Exp Brain Res. 1969;7(3):258–274. doi: 10.1007/BF00239033. [DOI] [PubMed] [Google Scholar]
  13. Schmidt R. F. Presynaptic inhibition in the vertebrate central nervous system. Ergeb Physiol. 1971;63:20–101. doi: 10.1007/BFb0047741. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Wallis D. I., Lees G. M., Kosterlitz H. W. Recording resting and action potentials by the sucrose-gap method. Comp Biochem Physiol C. 1975 Apr 1;50(2):199–216. [PubMed] [Google Scholar]
  16. Wallis D. I., North R. A. The action of 5-hydroxytryptamine on single neurones of the rabbit superior cervical ganglion. Neuropharmacology. 1978 Dec;17(12):1023–1028. doi: 10.1016/0028-3908(78)90028-x. [DOI] [PubMed] [Google Scholar]
  17. Wallis D. I., Woodward B. Membrane potential changes induced by 5-hydroxytryptamine in the rabbit superior cervical ganglion. Br J Pharmacol. 1975 Oct;55(2):199–212. doi: 10.1111/j.1476-5381.1975.tb07629.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wallis D. I., Woodward B. Proceedings: The depolarizing action of 5-hydroxytryptamine on sympathetic ganglion cells. Br J Pharmacol. 1973 Sep;49(1):168P–168P. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES