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. 1980 Feb;68(2):321–332. doi: 10.1111/j.1476-5381.1980.tb10421.x

Comparison of mianserin with desipramine, maprotiline and phentolamine on cardiac presynaptic and vascular postsynaptic α-adrenoceptors and noradrenaline reuptake in pithed normotensive rats

I Cavero, R Gomeni, Françoise Lefèvre-Borg, AG Roach
PMCID: PMC2043925  PMID: 6244040

Abstract

1 The cardiovascular effects of intravenous desipramine (0.03 and 0.1 mg/kg), maprotiline (0.5 mg/kg), mianserin (1.0 and 3.0 mg/kg) and phentolamine (0.25 mg/kg) were examined and compared in pithed rats. Several experimental procedures were used in order to distinguish between the effects of the compounds on cardiac presynaptic α-adrenoceptors and on neuronal noradrenaline reuptake, as inhibition of either mechanism produces an increase of neurotransmitter concentration within the sympathetic synapse and therefore results in a greater end organ response.

2 Pressor responses elicited by noradrenaline were potentiated by desipramine and maprotiline, reduced by phentolamine and not significantly modified by mianserin. However, all four compounds inhibited the pressor action of tyramine. Furthermore, mianserin reduced the pressor response to adrenaline.

3 Desipramine, maprotiline and mianserin, but not phentolamine enhanced the positive chronotropic effects of noradrenaline, without affecting those of isoprenaline.

4 All four compounds abolished the clonidine-induced inhibition of heart rate responses to short term electrical stimulation of the spinal cord. Moreover, in rats with a persistent tachycardia (induced by continuous stimulation of the thoracic spinal cord) desipramine, maprotiline and mianserin further increased heart rate. This effect was also observed in animals pretreated with phentolamine, administered in order to inhibit cardiac presynaptic α-adrenoceptors.

5 In rats with a sustained tachycardia (100 beats/min produced by electrical stimulation of the spinal cord) both mianserin and phentolamine, in contrast to desipramine, shifted the clonidine heart rate dose-response curve to the right. Phentolamine was about 34 times more potent than mianserin in this respect.

6 In pithed, reserpine-treated rats, the pressor responses to clonidine were not significantly modified by desipramine. The dose-response curves were shifted to the right by phentolamine (0.25 mg/kg) and mianserin (3.0 mg/kg).

7 These results indicate that mianserin is an antagonist of both cardiac presynaptic and vascular postsynaptic α-adrenoceptors and also inhibits the neuronal reuptake of noradrenaline.

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Selected References

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

  1. Arbilla S., Langer S. Z. Differences between presynaptic and postsynaptic alpha-adrenoceptors in the isolated nictitating membrane of the cat: effects of metanephrine and tolazoline. Br J Pharmacol. 1978 Oct;64(2):259–264. doi: 10.1111/j.1476-5381.1978.tb17298.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Autret A. M., Schmitt H., Fenard S., Pétillot N. Comparison of haemodynamic effects of alpha-sympathomimetic drugs. Eur J Pharmacol. 1971 Jan;13(2):208–217. doi: 10.1016/0014-2999(71)90152-x. [DOI] [PubMed] [Google Scholar]
  3. Baumann P. A., Maître L. Blockade of presynaptic alpha-receptors and of amine uptake in the rat brain by the antidepressant mianserine. Naunyn Schmiedebergs Arch Pharmacol. 1977 Oct;300(1):31–37. doi: 10.1007/BF00505077. [DOI] [PubMed] [Google Scholar]
  4. Brogden R. N., Heel R. C., Speight T. M., Avery G. S. Mianserin: a review of its pharmacological properties and therapeutic efficacy in depressive illness. Drugs. 1978 Oct;16(4):273–301. doi: 10.2165/00003495-197816040-00001. [DOI] [PubMed] [Google Scholar]
  5. Brunner H., Hedwall P. R., Meier M., Bein H. J. Cardiovascular effects of preparation CIBA 34,276-Ba and imipramine. Agents Actions. 1971 Aug;2(2):69–82. doi: 10.1007/BF01990085. [DOI] [PubMed] [Google Scholar]
  6. Cavero I., Gomeni R., Lefèvre-Borg F., Roach A. G. Effects of mianserin on noradrenaline uptake, cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors in rats [proceedings]. Br J Pharmacol. 1979 May;66(1):132P–133P. [PMC free article] [PubMed] [Google Scholar]
  7. Doxey J. C., Everitt J. Inhibitory effects of clonidine on responses to sympathetic nerve stimulation in the pithed rat. Br J Pharmacol. 1977 Dec;61(4):559–566. doi: 10.1111/j.1476-5381.1977.tb07548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doxey J. C., Everitt J., Metcalf G. Mianserin--an analysis of its peripheral autonomic actions. Eur J Pharmacol. 1978 Sep 1;51(1):1–10. doi: 10.1016/0014-2999(78)90055-9. [DOI] [PubMed] [Google Scholar]
  9. Goodlet I., Mireylees S. E., Sugrue M. F. Effects of mianserin, a new antidepressant, on the in vitro and in vivo uptake of monoamines. Br J Pharmacol. 1977 Oct;61(2):307–313. doi: 10.1111/j.1476-5381.1977.tb08420.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goodlet I., Sugrue M. F. Proceedings: The effects of a new anti-depressant, ORG GB94, on amine uptake mechanisms. Br J Pharmacol. 1974 Nov;52(3):431P–431P. [PMC free article] [PubMed] [Google Scholar]
  11. Harper B., Hughes I. E. A comparison in rabbit isolated hearts of the dysrhythmogenic potential of amitriptyline, maprotiline and mianserin in relation to their ability to block noradrenaline uptake. Br J Pharmacol. 1977 Apr;59(4):651–660. doi: 10.1111/j.1476-5381.1977.tb07734.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kafoe W. F., Leonard B. E. The effect of a new tetracyclic anti-depressant compound, Org GB 94, on the turnover of dopamine, noradrenalin and serotonin in the rat brain. Arch Int Pharmacodyn Ther. 1973 Dec;206(2):389–391. [PubMed] [Google Scholar]
  13. Langer S. Z. Sixth gaddum memorial lecture, National Institute for Medical Research, Mill Hill, January 1977. Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol. 1977 Aug;60(4):481–497. doi: 10.1111/j.1476-5381.1977.tb07526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maître L., Staehelin M., Bein H. J. Blockade of noradrenaline uptake by 34276-Ba, a new antidepressant drug. Biochem Pharmacol. 1971 Sep;20(9):2169–2186. doi: 10.1016/0006-2952(71)90216-4. [DOI] [PubMed] [Google Scholar]
  15. Pinder R. M., Brogden R. N., Speight T. M., Avery G. S. Maprotiline: a review of its pharmacological properties and therapeutic efficacy in mental depressive states. Drugs. 1977 May;13(5):321–352. doi: 10.2165/00003495-197713050-00001. [DOI] [PubMed] [Google Scholar]
  16. Raiteri M., Angelini F., Bertollini A. Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes. J Pharm Pharmacol. 1976 Jun;28(6):483–488. doi: 10.1111/j.2042-7158.1976.tb02770.x. [DOI] [PubMed] [Google Scholar]
  17. Roach A. G., Lefèvre F., Cavero I. Effects of prazosin and phentolamine on cardiac presynaptic alpha-adrenoceptors in the cat, dog and rat. Clin Exp Hypertens. 1978;1(1):87–101. doi: 10.3109/10641967809068597. [DOI] [PubMed] [Google Scholar]
  18. Robson R. D., Antonaccio M. J., Saelens J. K., Liebman J. Antagonism by mianserin and classical alpha-adrenoceptor blocking drugs of some cardiovascular and behavioral effects of clonidine. Eur J Pharmacol. 1978 Feb 15;47(4):431–442. doi: 10.1016/0014-2999(78)90124-3. [DOI] [PubMed] [Google Scholar]
  19. Starke K. Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol. 1977;77:1–124. doi: 10.1007/BFb0050157. [DOI] [PubMed] [Google Scholar]
  20. Vargaftig B. B., Coignet J. L., de Vos C. J., Grijsen H., Bonta I. L. Mianserin hydrochloride: peripheral and central effects in relation to antagonism against 5-hydroxytryptamine and tryptamine. Eur J Pharmacol. 1971 Nov-Dec;16(3):336–346. doi: 10.1016/0014-2999(71)90036-7. [DOI] [PubMed] [Google Scholar]
  21. Westfall T. C. Local regulation of adrenergic neurotransmission. Physiol Rev. 1977 Oct;57(4):659–728. doi: 10.1152/physrev.1977.57.4.659. [DOI] [PubMed] [Google Scholar]
  22. van Riezen H. Different central effects of the 5-HT antagonists mianserine and cyproheptadine. Arch Int Pharmacodyn Ther. 1972 Aug;198(2):256–269. [PubMed] [Google Scholar]
  23. van Zwieten P. A. Interaction between centrally acting hypotensive drugs and tricyclic antidepressants. Arch Int Pharmacodyn Ther. 1975 Mar;214(1):12–30. [PubMed] [Google Scholar]

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