Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1983 Aug;79(4):915–922. doi: 10.1111/j.1476-5381.1983.tb10536.x

Effects of LM 5008, a selective inhibitor of 5-hydroxytryptamine uptake, on blood pressure and responses to sympathomimetic amines.

R Ashkenazi, J P Finberg, M B Youdim
PMCID: PMC2044950  PMID: 6652362

Abstract

LM 5008 (4-[2-(3-indolyl)ethyl]piperidine) (10, 20 and 50 mg kg-1) had no significant effect on pressor responses to noradrenaline or tyramine in rats anaesthetized with urethane. Desmethylimipramine (1 mg kg-1) blocked the response to tyramine but chlorimipramine (5 mg kg-1) had no significant effect on responses to noradrenaline or tyramine. In the rabbit, anaesthetized with chloralose, LM 5008 (5 mg kg-1) had no effect on pressor responses to noradrenaline, tyramine or angiotensin II, while desmethylimipramine (0.25 mg kg-1) inhibited responses to tyramine and potentiated those to noradrenaline. LM 5008 (10 mg kg-1) had no effect on resting blood pressure of conscious normotensive or DOCA-saline hypertensive rats. Tranylcypromine (5 mg kg-1) produced a fall in blood pressure in conscious normotensive and in DOCA hypertensive rats. Treatment with a combination of LM 5008 (10 mg kg-1) and tranylcypromine (5 mg kg-1) resulted in the appearance of a behavioural hyperactivity syndrome, but blood pressure was not different from that of animals treated with tranylcypromine alone. These results further demonstrate the selectivity of LM 5008 for 5-hydroxytryptamine as opposed to catecholamine uptake.

Full text

PDF
919

Selected References

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

  1. Antonaccio M. J., Robson R. D. Cardiovascular effects of 5-hydroxytryptophan in anaesthetized dogs. J Pharm Pharmacol. 1973 Jun;25(6):495–497. doi: 10.1111/j.2042-7158.1973.tb09142.x. [DOI] [PubMed] [Google Scholar]
  2. Baum T., Shropshire A. T. Inhibition of efferent sympathetic nerve activity by 5-hydroxytryptophan and centrally administered 5-hydroxytryptamine. Neuropharmacology. 1975 Mar;14(3):227–233. doi: 10.1016/0028-3908(75)90010-6. [DOI] [PubMed] [Google Scholar]
  3. Buckingham R. E., Hamilton T. C., Robson D. Effect of intracerebroventricular 5,6-dihydroxytryptamine on blood pressure of spontaneously hypertensive rats. Eur J Pharmacol. 1976 Apr;36(2):431–437. doi: 10.1016/0014-2999(76)90097-2. [DOI] [PubMed] [Google Scholar]
  4. Chalmers J. P., Wing L. M. Central serotonin and cardiovascular control. Clin Exp Pharmacol Physiol. 1975;Suppl 2:195–200. [PubMed] [Google Scholar]
  5. Dunkley B., Sanghvi I., Friedman E., Gershion S. Comparison of behavioral and cardiovascular effects of L-DOPA and 5-HTP in conscious dogs. Psychopharmacologia. 1972;26(2):161–172. doi: 10.1007/BF00422103. [DOI] [PubMed] [Google Scholar]
  6. Echizen H., Freed C. R. Long-term infusion of L-5-hydroxytryptophan increases brain serotonin turnover and decreases blood pressure in normotensive rats. J Pharmacol Exp Ther. 1982 Mar;220(3):579–584. [PubMed] [Google Scholar]
  7. Finch L. The cardiovascular effects of intraventricular 5,6-dihydroxytryptamine in conscious hypertensive rats. Clin Exp Pharmacol Physiol. 1975 Nov-Dec;2(6):503–508. doi: 10.1111/j.1440-1681.1975.tb01855.x. [DOI] [PubMed] [Google Scholar]
  8. Flórez J., Armijo J. A. Effect of central inhibition of the 1-amino acid decarboxylase on the hypotensive action of 5-HT precursors in cats. Eur J Pharmacol. 1974 Apr;26(1):108–110. doi: 10.1016/0014-2999(74)90080-6. [DOI] [PubMed] [Google Scholar]
  9. Fuller R. W., Holland D. R., Yen T. T., Bemis K. G., Stamm N. B. Antihypertensive effects of fluoxetine and L-5-hydroxytryptophan in rats. Life Sci. 1979 Oct 1;25(14):1237–1242. doi: 10.1016/0024-3205(79)90466-1. [DOI] [PubMed] [Google Scholar]
  10. Fuller R. W., Yen T. T., Stamm N. B. Lowering of blood pressure by direct- and indirect-acting serotonin agonists in spontaneously hypertensive rats. Clin Exp Hypertens. 1981;3(3):497–508. doi: 10.3109/10641968109033678. [DOI] [PubMed] [Google Scholar]
  11. GREEN D. M., SAUNDERS F. J., WAHLGREN N., CRAIG R. L. Self-sustaining, post-DCA hypertensive cardiovascular disease. Am J Physiol. 1952 Jul;170(1):94–106. doi: 10.1152/ajplegacy.1952.170.1.94. [DOI] [PubMed] [Google Scholar]
  12. Ghose K. Assessment of Peripheral adrenergic activity and its interactions with drugs in man. Eur J Clin Pharmacol. 1980 Apr;17(4):233–238. doi: 10.1007/BF00625795. [DOI] [PubMed] [Google Scholar]
  13. Göthert M., Klupp N. Cardiovascular effects of neurotoxic indolethylamines. Ann N Y Acad Sci. 1978 Jun 12;305:457–477. doi: 10.1111/j.1749-6632.1978.tb31541.x. [DOI] [PubMed] [Google Scholar]
  14. Hendley E. D., Snyder S. H. Relationship between the action of monoamine oxidase inhibitors on the noradrenaline uptake system and their antidepressant efficacy. Nature. 1968 Dec 28;220(5174):1330–1331. doi: 10.1038/2201330a0. [DOI] [PubMed] [Google Scholar]
  15. Henning M., Rubenson A. Effects of 5-hydroxytryptophan on arterial blood pressure, body temperature and tissue monoamines in the rat. Acta Pharmacol Toxicol (Copenh) 1971;29(23):145–154. doi: 10.1111/j.1600-0773.1971.tb00601.x. [DOI] [PubMed] [Google Scholar]
  16. Jarrott B., McQueen A., Graf L., Louis W. J. Serotonin levels in vascular tissue and the effects of a serotonin synthesis inhibitor on blood pressure in hypertensive rats. Clin Exp Pharmacol Physiol. 1975;Suppl 2:201–205. [PubMed] [Google Scholar]
  17. Kellams J. J., Klapper M. H., Small J. G. Trazodone, a new antidepressant: efficacy and safety in endogenous depression. J Clin Psychiatry. 1979 Sep;40(9):390–395. [PubMed] [Google Scholar]
  18. Krstić M. K., Djurković D. Analysis of cardiovascular responses to central administration of 5-hydroxytryptamine in rats. Neuropharmacology. 1980 May;19(5):455–463. doi: 10.1016/0028-3908(80)90053-2. [DOI] [PubMed] [Google Scholar]
  19. Kuhn D. M., Wolf W. A., Lovenberg W. Review of the role of the central serotonergic neuronal system in blood pressure regulation. Hypertension. 1980 May-Jun;2(3):243–255. doi: 10.1161/01.hyp.2.3.243. [DOI] [PubMed] [Google Scholar]
  20. Larochelle P., Hamet P., Enjalbert M. Responses to tyramine and norepinephrine after imipramine and trazodone. Clin Pharmacol Ther. 1979 Jul;26(1):24–30. doi: 10.1002/cpt197926124. [DOI] [PubMed] [Google Scholar]
  21. Le Fur G., Uzan A. Effects of 4-(3-indolyl-alkyl)piperidine derivatives on uptake and release of noradrenaline, dopamine and 5-hydroxytryptamine in rat brain synaptosomes, rat heart and human blood platelets. Biochem Pharmacol. 1977 Mar 15;26(6):497–503. doi: 10.1016/0006-2952(77)90324-0. [DOI] [PubMed] [Google Scholar]
  22. Lesse S. Tranylcypromine (Parnate)--a study of 1000 patients with severe agitated depressions. Am J Psychother. 1978 Apr;32(2):220–242. doi: 10.1176/appi.psychotherapy.1978.32.2.220. [DOI] [PubMed] [Google Scholar]
  23. Nava-Félix P., Hong E. Nature of the central serotonin receptors mediating hypotension. J Cardiovasc Pharmacol. 1979 Jul-Aug;1(4):461–466. doi: 10.1097/00005344-197907000-00008. [DOI] [PubMed] [Google Scholar]
  24. Rao G. H., Einzig S., Reddy K. R., White J. G. Tranylcypromine induced hypertension is not mediated by the inhibition of prostacyclin synthesis. Prostaglandins Med. 1979 Oct;3(4):201–210. doi: 10.1016/0161-4630(79)90081-8. [DOI] [PubMed] [Google Scholar]
  25. Ross S. B., Ogren S. O., Renyi A. L. (Z)-dimethylamino-1-(4-bromophenyl)-1-(3-pyridyl) propene (h 102/09), a new selective inhibitor of the neuronal 5-hydroxytryptamine uptake. Acta Pharmacol Toxicol (Copenh) 1976 Aug;39(2):152–166. doi: 10.1111/j.1600-0773.1976.tb03166.x. [DOI] [PubMed] [Google Scholar]
  26. Ross S. B., Renyi A. L. Tricyclic antidepressant agents. I. Comparison of the inhibition of the uptake of 3-H-noradrenaline and 14-C-5-hydroxytryptamine in slices and crude synaptosome preparations of the midbrain-hypothalamus region of the rat brain. Acta Pharmacol Toxicol (Copenh) 1975;36(Suppl 5):382–394. doi: 10.1111/j.1600-0773.1975.tb00806.x. [DOI] [PubMed] [Google Scholar]
  27. Sethna E. R. A study of refractory cases of depressive illnesses and their response to combined antidepressant treatment. Br J Psychiatry. 1974 Mar;124(0):265–272. doi: 10.1192/bjp.124.3.265. [DOI] [PubMed] [Google Scholar]
  28. Smits J. F., Struyker-Boudier H. A. Intrahypothalamic serotonin and cardiovascular control in rats. Brain Res. 1976 Jul 30;111(2):422–427. doi: 10.1016/0006-8993(76)90788-5. [DOI] [PubMed] [Google Scholar]
  29. Tadepalli A. S., Mills E., Schanberg S. M. Central depression of carotid baroreceptor pressor response, arterial pressure and heart rate by 5-hydroxytryptophan: influence of supracollicular areas of the brain. J Pharmacol Exp Ther. 1977 Aug;202(2):310–319. [PubMed] [Google Scholar]
  30. Waldmeier P. C., Baumann P. A., Maítre L. CGP 6085 A, a new, specific, inhibitor of serotonin uptake: neurochemical characterization and comparison with other serotonin uptake blockers. J Pharmacol Exp Ther. 1979 Oct;211(1):42–49. [PubMed] [Google Scholar]
  31. Wenting G. J., Man in 't Veld A. J., Woittiez A. J., Boomsma F., Schalekamp M. A. Treatment of hypertension with ketanserin, a new selective 5-HT2 receptor antagonist. Br Med J (Clin Res Ed) 1982 Feb 20;284(6315):537–539. doi: 10.1136/bmj.284.6315.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Young J. P., Lader M. H., Hughes W. C. Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients. Br Med J. 1979 Nov 24;2(6201):1315–1317. doi: 10.1136/bmj.2.6201.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES