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. 1983 Jun;79(2):401–407. doi: 10.1111/j.1476-5381.1983.tb11012.x

Effect of 781094, a new selective alpha-adrenoceptor antagonist, on the aggregatory responses of human blood platelets and on binding of [3H]-dihydroergocryptine to these cells.

R Kerry, M C Scrutton
PMCID: PMC2044865  PMID: 6140040

Abstract

781094 (2-(2(1, 4-benzodioxanyl))-2-imidazoline hydrochloride) is a potent competitive inhibitor of the aggregatory responses of human platelets induced by adrenaline (pA2 = 7.3) and UK-14304. 781094 is a more potent inhibitor of the pro-aggregatory response to clonidine than of that to methoxamine. The alpha 2/alpha 1-adrenoceptor selectivity ratio is 11.4. 781094 is a potent inhibitor of the binding of [3H]-dihydroergocryptine to platelet lysates. 781094 has no effect on the aggregatory responses of human platelets induced by adenosine-5'-pyrophosphate (ADP), 5-hydroxytryptamine, thrombin, U-46619, or arginine-vasopressin provided that the platelet-rich plasma does not exhibit enhanced responsiveness. In some instances high concentrations of 781094 potentiate the aggregatory response to collagen. In platelet-rich plasma which exhibits enhanced responsiveness, 781094 causes partial inhibition of the aggregatory responses to 5-hydroxytryptamine, ADP and vasopressin at concentrations similar to those required to inhibit the response to adrenaline. 781094 acts as a specific antagonist for the responses mediated by human platelet alpha-adrenoceptors and exhibits moderate selectivity for the alpha 2-adrenoceptors on this cell.

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ASTER R. H., JANDL J. H. PLATELET SEQUESTRATION IN MAN. I. METHODS. J Clin Invest. 1964 May;43:843–855. doi: 10.1172/JCI104970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashton H., Rawlins M. D. Central nervous system depressant actions of clonidine and UK-14,304: partial dissociation of EEG and behavioural effects. Br J Clin Pharmacol. 1978 Feb;5(2):135–140. doi: 10.1111/j.1365-2125.1978.tb01614.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Besterman E. M., Gillett M. P. Influence of lysolecithin on platelet aggregation initiated by 5-hydroxytryptamine. Nat New Biol. 1973 Feb 14;241(111):223–224. doi: 10.1038/newbio241223a0. [DOI] [PubMed] [Google Scholar]
  5. Cambridge D. UK-14,304, a potent and selective alpha2-agonist for the characterisation of alpha-adrenoceptor subtypes. Eur J Pharmacol. 1981 Jul 10;72(4):413–415. doi: 10.1016/0014-2999(81)90588-4. [DOI] [PubMed] [Google Scholar]
  6. Cheng Y., Prusoff W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973 Dec 1;22(23):3099–3108. doi: 10.1016/0006-2952(73)90196-2. [DOI] [PubMed] [Google Scholar]
  7. Da Prada M., Zürcher Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci. 1976 Oct 15;19(8):1161–1174. doi: 10.1016/0024-3205(76)90251-4. [DOI] [PubMed] [Google Scholar]
  8. Grant J. A., Scrutton M. C. Interaction of selective alpha-adrenoceptor agonists and antagonists with human and rabbit blood platelets. Br J Pharmacol. 1980;71(1):121–134. doi: 10.1111/j.1476-5381.1980.tb10917.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grant J. A., Scrutton M. C. Novel alpha2-adrenoreceptors primarily responsible for inducing human platelet aggregation. Nature. 1979 Feb 22;277(5698):659–661. doi: 10.1038/277659a0. [DOI] [PubMed] [Google Scholar]
  10. Hsu C. Y., Knapp D. R., Halushka P. V. The effects of alpha adrenergic agents on human platelet aggregation. J Pharmacol Exp Ther. 1979 Mar;208(3):366–370. [PubMed] [Google Scholar]
  11. Knight D. E., Scrutton M. C. Direct evidence for a role for Ca2+ in amine storage granule secretion by human platelets. Thromb Res. 1980 Nov 15;20(4):437–446. doi: 10.1016/0049-3848(80)90282-0. [DOI] [PubMed] [Google Scholar]
  12. Newman K. D., Williams L. T., Bishopric N. H., Lefkowitz R. J. Identification of alpha-adrenergic receptors in human platelets by [3H]dihydroergocryptine binding. J Clin Invest. 1978 Feb;61(2):395–402. doi: 10.1172/JCI108950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pearce P. H., Wright J. M., Egan C. M., Scrutton M. C. Interaction of human blood platelets with the 2',3'-dialdehyde and 2',3'-dialcohol derivatives of adenosine 5'-diphosphate and adenosine 5'-triphosphate. Eur J Biochem. 1978 Aug 1;88(2):543–554. doi: 10.1111/j.1432-1033.1978.tb12480.x. [DOI] [PubMed] [Google Scholar]
  14. Reid J. L., Jones D. H., Dollery C. T. Plasma-catecholamines in phaeochromocytoma. Lancet. 1976 Nov 6;2(7993):1021–1021. doi: 10.1016/s0140-6736(76)90853-9. [DOI] [PubMed] [Google Scholar]
  15. White J. G. A biphasic response of platelets to serotonin. Scand J Haematol. 1970;7(3):145–151. doi: 10.1111/j.1600-0609.1970.tb01881.x. [DOI] [PubMed] [Google Scholar]

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