Skip to main content
PMC home page
British Journal of Pharmacology and Chemotherapy logoLink to British Journal of Pharmacology and Chemotherapy
. 1963 Apr;20(2):362–377. doi: 10.1111/j.1476-5381.1963.tb01475.x

Mechanism of the initial adrenergic effects of bretylium and guanethidine

S D Gokhale, O D Gulati, V V Kelkar
PMCID: PMC1703630  PMID: 13948620

Abstract

Treatment with phenoxybenzamine and dichloroisoprenaline prevented the rise of blood pressure, contraction of the nictitating membrane and increase in cardiac contractile force produced by intravenous injections of bretylium and guanethidine in anaesthetized or spinal cats. Treatment with cocaine, imipramine or reserpine reduced the sensitivity to bretylium and guanethidine of the spinal cat. In the spinal cat treated with reserpine, sensitivity to the drugs could be restored by an infusion of noradrenaline. Chlorpromazine also blocked the pressor and nictitating membrane responses to bretylium and guanethidine. The drug effects were unaltered 1 hr after bilateral adrenalectomy. During the intravenous infusion of noradrenaline into spinal cats the pressor responses to bretylium and guanethidine were increased, whilst those to adrenaline and to noradrenaline were decreased. Guanethidine (3 to 5 mg/kg) injected intravenously into the cat caused a sudden relaxation of the rat isolated stomach-strip bathed in blood. In seven similar experiments bretylium (3 to 5 mg/kg) relaxed the strip only once; in the other six experiments there was either no effect (four experiments) or an increase in the tone of the strip (two experiments). It is concluded that the initial adrenergic effects of bretylium and guanethidine are mediated, at least in part, through a release of catechol amines from stores in the effector organ.

Full text

PDF
376

Selected References

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

  1. ATHOS W. J., McHUGH B. P., FINEBERG S. E., HILTON J. G. The effects of guanethidine on the adrenal medulla. J Pharmacol Exp Ther. 1962 Aug;137:229–234. [PubMed] [Google Scholar]
  2. AVIADO D. M., DIL A. H. The effects of a new sympathetic blocking drug (bretylium) on cardiovascular control. J Pharmacol Exp Ther. 1960 Jul;129:328–337. [PubMed] [Google Scholar]
  3. AXELROD J., WEIL-MALHERBE H., TOMCHICK R. The physiological disposition of H3-epinephrine and its metabolite metanephrine. J Pharmacol Exp Ther. 1959 Dec;127:251–256. [PubMed] [Google Scholar]
  4. BOURA A. L., GREEN A. F. The actions of bretylium: adrenergic neurone blocking and other effects. Br J Pharmacol Chemother. 1959 Dec;14:536–548. doi: 10.1111/j.1476-5381.1959.tb00961.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BURN J. H. A new view of adrenergic nerve fibres, explaining the action of reserpine, bretylium, and guanethidine. Br Med J. 1961 Jun 10;1(5240):1623–1627. doi: 10.1136/bmj.1.5240.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BURN J. H., RAND M. J. The action of sympathomimetic amines in animals treated with reserpine. J Physiol. 1958 Dec 4;144(2):314–336. doi: 10.1113/jphysiol.1958.sp006104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. BUTTERFIELD J. L., RICHARDSON J. A. Acute effects of guanethidine on myocardial contractility and catecholamine levels. Proc Soc Exp Biol Med. 1961 Feb;106:259–262. doi: 10.3181/00379727-106-26303. [DOI] [PubMed] [Google Scholar]
  8. CASS R., KUNTZMAN R., BRODIE B. B. Norepinephrine depletion as a possible mechanism of action of guanethidine (SU 5864), a new hypotensive agent. Proc Soc Exp Biol Med. 1960 Apr;103:871–872. doi: 10.3181/00379727-103-25702. [DOI] [PubMed] [Google Scholar]
  9. DRESSE A., SODOYEZ J. C. [Effect of guanethidine on arterial pressure and on the uterus of the rat]. C R Seances Soc Biol Fil. 1960;154:2399–2401. [PubMed] [Google Scholar]
  10. EHRINGER H., HORNYKIEWICZ O., LECHNER K. [The effect of chlorpromazine on catecholamine and 5-hydroxytryptamine metabolism in the rat brain]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1960;239:507–519. [PubMed] [Google Scholar]
  11. FLECKENSTEIN A., BURN J. H. The effect of denervation on the action of sympathomimetic amines on the nictitating membrane. Br J Pharmacol Chemother. 1953 Mar;8(1):69–78. doi: 10.1111/j.1476-5381.1953.tb00754.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. FLECKENSTEIN A., STOCKLE D. Zum Mechanismus der Wirkungs-Verstärkung und Wirkungs-Abschwächung sympathomimetischer Amine durch Cocain und andere Pharmaka. II. Die Hemmung der Neuro-Sympathomimetica durch Cocain. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1955;224(5-6):401–415. [PubMed] [Google Scholar]
  13. FLEMING W. W., TRENDELENBURG U. The development of supersensitivity to norepinephrine after pretreatment with reserpine. J Pharmacol Exp Ther. 1961 Jul;133:41–51. [PubMed] [Google Scholar]
  14. GILLIS C. N., NASH C. W. The initial pressor actions of bretylium tosylate and guanethidine sulfate and their relation to release of catecholamines. J Pharmacol Exp Ther. 1961 Oct;134:1–7. [PubMed] [Google Scholar]
  15. GOKHALE S. D., GULATI O. D. Potentiation of inhibitory and excitatory effects of catechol amines by bretylium. Br J Pharmacol Chemother. 1961 Jun;16:327–334. doi: 10.1111/j.1476-5381.1961.tb01092.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. HERTING G., AXELROD J., WHITBY L. G. Effect of drugs on the uptake and metabolism of H3-norepinephrine. J Pharmacol Exp Ther. 1961 Nov;134:146–153. [PubMed] [Google Scholar]
  17. HERTTING G., AXELROD J., PATRICK R. W. Actions of bretylium and guanethidine on the uptake and release of [3H]-noradrenaline. Br J Pharmacol Chemother. 1962 Feb;18:161–166. doi: 10.1111/j.1476-5381.1962.tb01159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. KADZIELAWA K. Mechanism of action of guanethidine. Br J Pharmacol Chemother. 1962 Aug;19:74–84. doi: 10.1111/j.1476-5381.1962.tb01428.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. LOCKETT M. F., EAKINS K. E. Chromatographic studies of the effect of intravenous injections of tyramine on the concentrations of adrenaline and noradrenaline in plasma. J Pharm Pharmacol. 1960 Sep;12:513–517. doi: 10.1111/j.2042-7158.1960.tb12702.x. [DOI] [PubMed] [Google Scholar]
  20. LOCKETT M. F., EAKINS K. E. The release of sympathetic amines by tyramine from the aortic walls of cats. J Pharm Pharmacol. 1960 Dec;12:720–725. doi: 10.1111/j.2042-7158.1960.tb12737.x. [DOI] [PubMed] [Google Scholar]
  21. MAXWELL R. A., MULL R. P., PLUMMER A. J. [2-Octahydro-1-azocinyl)-ethyl]-guanidine sulfate (CIBA 5864-SU), a new synthetic antithypertensive agents]. Experientia. 1959 Jul 15;15:267–267. doi: 10.1007/BF02158076. [DOI] [PubMed] [Google Scholar]
  22. NASMYTH P. A. An investigation of the action of tyramine and its interrelationship with the effects of other sympathomimetic amines. Br J Pharmacol Chemother. 1962 Feb;18:65–75. doi: 10.1111/j.1476-5381.1962.tb01151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. PAGE I. H., DUSTAN H. P. A new, potent antihypertensive drug: preliminary study of [2-(octahydro-1-azocinyl)-ethyl]-guanidine sulfate (guanethidine). J Am Med Assoc. 1959 Jul 11;170(11):1265–1271. doi: 10.1001/jama.1959.03010110013003. [DOI] [PubMed] [Google Scholar]
  24. PATEL D. G., GULATI O. D., GOKHALE S. D. Cardiac actions of ganglion blocking and certain other drugs. Arch Int Pharmacodyn Ther. 1962 Jun 1;137:348–357. [PubMed] [Google Scholar]
  25. PLETSCHER A., GEY K. F. [The effect of chlorpromazine on the pharmacological changes of 5-hydroxytryptamine- and noradrenalin content in the brain]. Med Exp Int J Exp Med. 1960;2:259–265. [PubMed] [Google Scholar]
  26. REUSE J. J., BERGMANN F. [Pharmacodynamic properties of guanethidine]. C R Seances Soc Biol Fil. 1960;154:1536–1539. [PubMed] [Google Scholar]
  27. RICHARDSON D. W., WYSO E. M. Human pharmacology of guanethidine. Ann N Y Acad Sci. 1960 Oct 11;88:944–955. doi: 10.1111/j.1749-6632.1960.tb20086.x. [DOI] [PubMed] [Google Scholar]
  28. RYALL R. W. Effects of cocaine and antidepressant drugs on the nictitating membrane of the cat. Br J Pharmacol Chemother. 1961 Dec;17:339–357. doi: 10.1111/j.1476-5381.1961.tb01121.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. TRENDELENBURG U. Modification of the effect of tyramine by various agents and procedures. J Pharmacol Exp Ther. 1961 Oct;134:8–17. [PubMed] [Google Scholar]
  30. 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]
  31. WEINER N., DRASKOCZY P. R., BURACK W. R. The ability of tyramine to liberate catecholamines in vivo. J Pharmacol Exp Ther. 1962 Jul;137:47–55. [PubMed] [Google Scholar]
  32. WHITBY L. G., AXELROD J., WEIL-MALHERBE H. The fate of H3-norepinephrine in animals. J Pharmacol Exp Ther. 1961 May;132:193–201. [PubMed] [Google Scholar]

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

RESOURCES