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. 1987 Jul;24(1):96–99. doi: 10.1111/j.1365-2125.1987.tb03142.x

Thymoxamine: lack of antihistaminic effects in clinical doses in man.

S Al-Damluji, A Grossman, P Turner, G M Besser
PMCID: PMC1386286  PMID: 2956983

Abstract

The purpose of this study was to investigate whether the alpha 1-adrenoceptor antagonist thymoxamine possesses antihistaminic activity in clinical doses in man, as has been reported on the guinea pig ileum in vitro. Five normal subjects were given on three separate occasions intravenous infusions of thymoxamine (0.15 mg kg-1 loading dose followed by 0.15 mg kg-1 h-1), chlorpheniramine (1.5 mg loading dose followed by 1.5 mg h-1) and normal saline (placebo). Intravenous bolus doses of histamine (1 and 2 micrograms kg-1) were given after pretreatment with propranolol 10 mg to block the beta-adrenoceptor agonist effects of the catecholamines released by the histamine injections. Histamine caused a dose-dependent reduction of FEV1 and FVC that was antagonised by chlorpheniramine but not by thymoxamine, suggesting that thymoxamine has no antihistaminic activity in the doses used in man. Thymoxamine caused a small enhancement of the bronchoconstrictor effect of the lower dose of histamine. The relatively selective action of thymoxamine makes it a suitable agent for the investigation of alpha 1-adrenoceptors.

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Selected References

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

  1. Al-Damluji S., Cunnah D., Perry L., Grossman A., Besser G. M. The effect of alpha adrenergic manipulation on the 24 hour pattern of cortisol secretion in man. Clin Endocrinol (Oxf) 1987 Jan;26(1):61–66. doi: 10.1111/j.1365-2265.1987.tb03639.x. [DOI] [PubMed] [Google Scholar]
  2. Al-Damluji S., Perry L., Tomlin S., Bouloux P., Grossman A., Rees L. H., Besser G. M. Alpha-adrenergic stimulation of corticotropin secretion by a specific central mechanism in man. Neuroendocrinology. 1987 Jan;45(1):68–76. doi: 10.1159/000124705. [DOI] [PubMed] [Google Scholar]
  3. Bianco S., Griffin J. P., Kamburoff P. L., Prime F. J. The effect of thymoxamine on histamine induced bronchospasm in man. Br J Dis Chest. 1972 Jan;66(1):27–32. [PubMed] [Google Scholar]
  4. Birmingham A. T., Akubue P. I., Szolcsányi J. A quantitative analysis of the antagonism of intravenous noradrenaline by thymoxamine or phentolamine on the blood pressure of the conscious cat. J Pharm Pharmacol. 1967 Mar;19(3):137–145. doi: 10.1111/j.2042-7158.1967.tb08055.x. [DOI] [PubMed] [Google Scholar]
  5. Birmingham A. T., Szolcsányi J. Competitive blockade of adrenergic alpha-receptors and histamine receptors by thymoxamine. J Pharm Pharmacol. 1965 Jul;17(7):449–458. doi: 10.1111/j.2042-7158.1965.tb07701.x. [DOI] [PubMed] [Google Scholar]
  6. Brown R., Ingram R. H., Jr, Wellman J. J., McFadden E. R., Jr Effects of intravenous histamine on pulmonary mechanics in nonasthmatic and asthmatic subjects. J Appl Physiol Respir Environ Exerc Physiol. 1977 Feb;42(2):221–227. doi: 10.1152/jappl.1977.42.2.221. [DOI] [PubMed] [Google Scholar]
  7. Colebatch H. J., Engel L. A. Constriction of the lung by histamine before and after adrenalectomy in cats. J Appl Physiol. 1974 Dec;37(6):798–805. doi: 10.1152/jappl.1974.37.6.798. [DOI] [PubMed] [Google Scholar]
  8. Drew G. M. Effects of alpha-adrenoceptor agonists and antagonists on pre- and postsynaptically located alpha-adrenoceptors. Eur J Pharmacol. 1976 Apr;36(2):313–320. doi: 10.1016/0014-2999(76)90084-4. [DOI] [PubMed] [Google Scholar]
  9. Gaddie J., Legge J. S., Petrie G., Palmer K. N. The effect of an alpha-adrenergic receptor blocking drug on histamine sensitivity in bronchial asthma. Br J Dis Chest. 1972 Apr;66(2):141–146. [PubMed] [Google Scholar]
  10. Kerr J. W., Govindaraj M., Patel K. R. Effect of alpha-receptor blocking drugs and disodium cromoglyate on histamine hypersensitivity in bronchial asthma. Br Med J. 1970 Apr 18;2(5702):139–141. doi: 10.1136/bmj.2.5702.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mathé A. A., Aström A., Persson N. A. Some bronchoconstricting and bronchodilating responses of human isolated bronchi: evidence for the existence of -adrenoceptors. J Pharm Pharmacol. 1971 Dec;23(12):905–910. doi: 10.1111/j.2042-7158.1971.tb09891.x. [DOI] [PubMed] [Google Scholar]
  12. Newball H. H., Keiser H. R. Relative effects of bradykinin and histamine on the respiratory system of man. J Appl Physiol. 1973 Oct;35(4):552–556. doi: 10.1152/jappl.1973.35.4.552. [DOI] [PubMed] [Google Scholar]
  13. Pegelow K. O. Bronchial reactivity to inhaled histamine in asthmatic patients, before and after administration of atropine, phentolamine or disodium cromoglycate. Acta Allergol. 1974 Oct;29(5):365–384. doi: 10.1111/j.1398-9995.1974.tb01472.x. [DOI] [PubMed] [Google Scholar]
  14. Ploy-Song-Sand Y., Corbin R. P., Engel L. A. Effects of intravenous histamine on lung mechanics in man after beta-blockade. J Appl Physiol Respir Environ Exerc Physiol. 1978 May;44(5):690–695. doi: 10.1152/jappl.1978.44.5.690. [DOI] [PubMed] [Google Scholar]
  15. Smith R., Grossman A., Boyce M. J., Besser G. M., Rees L. H. Effect of histamine infusion on circulating methionine-enkephalin and catecholamine concentrations. Neurosci Lett. 1985 Apr 19;55(3):289–292. doi: 10.1016/0304-3940(85)90450-1. [DOI] [PubMed] [Google Scholar]

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