Abstract
1. In isolated rat mesentery preparations, intra-arterial injection of the following drugs rapidly suppressed vasoconstrictor responses to sympathetic nerve stimulation: bretylium (75-100 μg), guanethidine (10-20 μg) and bethanidine (20-30 μg); with phenoxypropylguanidine (15-30 μg) the onset of blockade was slower. The blockade caused by these or higher concentrations was rapidly abolished by intra-arterial injection of amphetamine (100 μg) as also was the blockade caused by infusing bretylium or guanethidine for 10-20 min. Partial blockade was produced by 20 μg of reserpine and this was only slightly and briefly antagonized by amphetamine.
2. In mesentery preparations taken from rats 24 h after subcutaneous injection of bretylium 50 mg/kg, guanethidine 10 mg/kg, phenoxypropylguanidine 10 mg/kg or reserpine 0·1 mg/kg, responses to sympathetic nerve stimulation were greatly impaired. Only in the preparations from the bretylium-treated rats did amphetamine antagonize the blockade. The adrenergic neurone blocking effect of bethanidine 10 mg/kg was evident at 12 h but not at 24 h after injection.
3. In rat mesentery amphetamine did not cause vasoconstriction but briefly potentiated the vasoconstrictor effect of sympathetic nerve stimulation. Responses to noradrenaline were not importantly affected.
4. The contractile responses of the rat inferior eyelid caused by stimulation of the cervical sympathetic nerve was greatly reduced 17-27 h after subcutaneous injection of bretylium 300 mg/kg, bethanidine 30 mg/kg, guanethidine 10 mg/kg or reserpine 0·3 mg/kg. Intravenous dexamphetamine (0·5 mg/kg) powerfully antagonized the effect of bretylium, weakly antagonized the blockade by bethanidine and guanethidine and caused no change in the response of reserpine-treated animals.
5. The vas deferens taken from guinea-pigs 24 h after subcutaneous injection of either bretylium or guanethidine showed greatly impaired responses to hypogastric nerve stimulation. Amphetamine largely restored the contractile response in bretylium-treated rats but caused only weak antagonism in the guanethidine-treated animals.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BENMILOUD M., VON EULERU EFFECTS OF BRETYLIUM, RESERPINE, GUANETHIDINE AND SYMPATHETIC DENERVATION ON THE NORADRENALINE CONTENT OF THE RAT SUBMAXILLARY GLAND. Acta Physiol Scand. 1963 Sep-Oct;59:34–42. doi: 10.1111/j.1748-1716.1963.tb02720.x. [DOI] [PubMed] [Google Scholar]
- BOURA A. L., GREEN A. F. ADRENERGIC NEURONE BLOCKING AGENTS. Annu Rev Pharmacol. 1965;5:183–212. doi: 10.1146/annurev.pa.05.040165.001151. [DOI] [PubMed] [Google Scholar]
- CASS R., SPRIGGS T. L. Tissue amine levels and sympathetic blockade after guanethidine and bretylium. Br J Pharmacol Chemother. 1961 Dec;17:442–450. doi: 10.1111/j.1476-5381.1961.tb01131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHEN G., ENSOR C. R., MCCARTHY D. A., MCLEAN J. R., CAMPBELL A. THE PHARMACOLOGY OF 3-PHENOXYPROPYLGUANIDINE. J Pharmacol Exp Ther. 1964 Mar;143:374–382. [PubMed] [Google Scholar]
- COSTA E., KUNTZMAN R., GESSA G. L., BRODIE B. B. Structural requirements for bretylium and guanethidine-like activity. Life Sci. 1962 Mar;1:75–80. doi: 10.1016/0024-3205(62)90032-2. [DOI] [PubMed] [Google Scholar]
- DAY M. D. Effect of sympathomimetic amines on the blocking action of guanethidine, bretylium and xylocholine. Br J Pharmacol Chemother. 1962 Apr;18:421–439. doi: 10.1111/j.1476-5381.1962.tb01421.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAY M. D., RAND M. J. Antagonism of guanethidine by dexamphetamine and other related sympathomimetic amines. J Pharm Pharmacol. 1962 Sep;14:541–549. doi: 10.1111/j.2042-7158.1962.tb11137.x. [DOI] [PubMed] [Google Scholar]
- DAY M. D., RAND M. J. Evidence for a competitive antagonism of guanethidine by dexamphetamine. Br J Pharmacol Chemother. 1963 Feb;20:17–28. doi: 10.1111/j.1476-5381.1963.tb01293.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GOKHALE S. D., GULATI O. D., JOSHI N. Y. ANTAGONISM OF THE BLOCKING ACTION OF BRETYLIUM AND GUANETHIDINE ON THE PRESSOR EFFECT OF PHYSOSTIGMINE IN THE RAT. Br J Pharmacol Chemother. 1965 Jun;24:624–631. doi: 10.1111/j.1476-5381.1965.tb01618.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerkens J. F., McCulloch M. W. Mechanism of the antagonism between guanethidine and dexamphetamine. Br J Pharmacol. 1969 Mar;35(3):563–572. doi: 10.1111/j.1476-5381.1969.tb08297.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MCGREGOR D. D. THE EFFECT OF SYMPATHETIC NERVE STIMULATION OF VASOCONSTRICTOR RESPONSES IN PERFUSED MESENTERIC BLOOD VESSELS OF THE RAT. J Physiol. 1965 Mar;177:21–30. doi: 10.1113/jphysiol.1965.sp007572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- RYD G. Protective effect of bretylium on noradrenaline stores in organs. Acta Physiol Scand. 1962 Sep;56:90–93. doi: 10.1111/j.1748-1716.1962.tb02484.x. [DOI] [PubMed] [Google Scholar]
- Robson R. D. The action of adrenergic neurone blocking agents and other drugs on the pressor responses of various agents in the anaesthetized rat. Br J Pharmacol Chemother. 1967 Feb;29(2):194–203. doi: 10.1111/j.1476-5381.1967.tb01952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spriggs T. L. Peripheral noradrenaline and adrenergic transmission in the rat. Br J Pharmacol Chemother. 1966 Jan;26(1):271–281. doi: 10.1111/j.1476-5381.1966.tb01830.x. [DOI] [PMC free article] [PubMed] [Google Scholar]