Bupropion does not antagonize cardiovascular actions of clonidine in normal subjects and sponteneously hypertensive rats

Luigl X. Cubaddu, Gilles Cloutier, Kirsten Gross, Richard Grippo, Laura Tanner, Leslie Lerea, Michael Shakarjian, Gall Knowlton, T. Kendall Harden, William Arerlishorat, John F. Rogers

Research output: Contribution to journalArticle

Abstract

Tricyclic antidepressants (TADS) are known to antagonize the hypotensive and sedative actions of clonidine. We compared the effects of bupropion and Imipramine pretreatment on the acute hypotensive and sedative actions of clonidine in eight normotensive male subjects in a randomized, double-blind crossover study. Pretreatment with bupropion, 100 mg by mouth three times a day for 9 days, had no effect on baseline supine blood pressure (BP) and heart rate (HR) and did not modify the hypotensive, bradycardic, and sedative actions of clonidine. Imipramine, 25 mg by mouth three times a day for 9 days, increased supine and standing HR and decreased standing systolic BP. In half the subjects the hypotensive action of clonidine was reduced 40% to 50% by imipramine. The specific binding of 3H-yohimbine to α2-receptors of platelet membranes was not affected by pretreatment with either antidepressant. In spontaneously hypertensive rats, 16 days of bupropion, 25 mg1kg subcutaneously, had no effect on baseline BP and HR and did not antagonize the hypotensive and bradycardic effects of clonidine, 5 mg1kg iv. Pretreatment with desipramine, 5 mglkg subcutaneously for 16 days, accelerated baseline HR and reduced cardiovascular actions of clonidine. These observations suggest that not all antidepressants antagonize the effects of clonidine. If the negative interaction between TADs and clonidine is a result of sensitivity of α2-receptors, these receptor changes are not the common denominator of antidepressant activity and may only be seen with TADs.

Original languageEnglish (US)
Pages (from-to)576-584
Number of pages9
JournalClinical pharmacology and therapeutics
Volume35
Issue number5
DOIs
StatePublished - May 1984

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Cubaddu, L. X., Cloutier, G., Gross, K., Grippo, R., Tanner, L., Lerea, L., Shakarjian, M., Knowlton, G., Harden, T. K., Arerlishorat, W., & Rogers, J. F. (1984). Bupropion does not antagonize cardiovascular actions of clonidine in normal subjects and sponteneously hypertensive rats. Clinical pharmacology and therapeutics, 35(5), 576-584. https://doi.org/10.1038/clpt.1984.80