Summary
The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
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References
Baumann PA, Maitre L (1977) Blockade of pre-synaptic alpha receptors and of amine uptake in the rat brain by the antidepressant mianserin. Naunyn-Schmiedebergs Arch Pharmacol 300: 31–37
Boyd GW, Fitz AE, Adamson AR, Peart WS (1969) Radioimmunoassay of determination of plasma renin activity. Lancet 1: 213–219
Briant RH, Reid JL, Dollery CT (1973) Interaction between clonidine and desipramine in man. Br Med J 1: 522–523
Delbarre B, Schmitt H (1971) Sedative effects of sympathomimetic drugs and their antagonism by adrenergic and cholinergic blocking drugs. Eur J Pharmacol 13: 356–363
Dollery CT, Davies DS, Draffan GH, Dargie HJ, Dean CR, Reid JL, Clare RA, Murray S (1976) Clinical pharmacology and pharmacokinetics of clonidine. Clin Pharmacol Ther 19: 11–17
Doxey JC, Everitt J, Metcalf G (1978) Mianserin — an analysis of its peripheral autonomic actions. Eur J Pharmacol 51: 1–10
Elliott HL, McLean K, Sumner DJ, Reid JL (1981) Pharmacodynamic studies on mianserin and its interaction with clonidine. Eur J Clin Pharmacol 21: 97–102
von Euler US, Lishajko F (1961) Improved technique for the fluorimetric estimation of catecholamines. Acta Physiol Scand 51: 348–356
Finch L, Hersom A, Hicks P (1975) The control of blood pressure by central adrenergic neurones. In: Davies DS, Reid JL (eds) Central action of drugs in the regulation of blood pressure. Pitmans, London, pp 66–177
Henry DP, Starman BJ, Johnson DG, Williams RH (1975) A sensitive radioenzymatic assay for norepinephrine in tissue and plasma. Life Sci 16: 375–384
Kobinger W, Walland A (1967) Investigations into the mechanism of the hypotensive effect of 2-(2,6-Dichlor phenylamino-) Imidazoline-HCl. Eur J Pharmacol 2: 155–162
Kopera H (1978) Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo. Br J Clin Pharmacol 5: 29S-34S
Montgomery S, McAuley R, Montgomery DB (1978) Relationship between mianserin plasma levels and antidepressant effect in a double-blind trial comparing a single night-time and divided daily dose regimens. Br J Clin Pharmacol 5: 71S-76S
Perry GF, Fitzsimmons B, Shapiro L, Irwin P (1978) Clinical study of mianserin, imiparamine and placebo in depression: blood level and MHPG correlations. Br J Clin Pharmacol 5: 35S-41S
Rand MJ, Rush M, Wilson S (1969) Some observations on the inhibition of salivation by ST155. Eur J Pharmacol 5: 168–172
Reid JL, Briant RH (1977) An interaction between desmethylimipramine and clonidine. In: Grahame-Smith (ed) Drug Interactions. McMillan, London, pp 231–238
Reid JL, Briant RH, Dollery CT (1973) Desmethylimipramine and the hypotensive action of clonidine in the rabbit. Life Sci 12: 459–467
Rubin P, McLean K, Reid JL (1980) A comparative study of automated blood pressure recorders. Postgrad Med J 56: 815–817
Schmitt H, Schmitt H (1969) Localisation of the hypotensive effect of 2-(2-6-Dichlorophenylamino)-2-Imidazoline hydrochloride. Eur J Pharmacol 6: 8–12
Schmitt H, Schmitt H, Boissier JR, Guidecilli JF, Fichelle J (1968) Cardiovascular effects of 2-(2,6-Dichlorphenylamino)-2-Imidazoline HCl. Eur J Pharmacol 2: 340–346
van Spanning HW, van Zwieten PA (1973) The interference of tricyclic antidepressants with the central hypotensive effect of clonidine. Eur J Pharmacol 24: 402–404
van Spanning HW, van Zwieten PA (1975) The interaction between alpha methyldopa and tricyclic antidepressants. Int J Clin Pharmacol 11: 65–67
Vargaftig BB, Coignet JL, de Vos CJ, Grijsen H, Bonta IL (1971) Mianserin hydrochloride: peripheral and central effects in relation to antagonism against 5-hydroxytryptamine and tryptamine. Eur J Pharmacol 16: 336–346
Vink J, Van Hal HJM (1980) Simplified method for the determination of the tetracyclic antidepressant mianserin in human plasma using gas chromatography with nitrogen detection. J Chromatogr 181: 25–31
White AG (1965) Methyldopa and amitriptyline. Lancet 1: 441
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Elliott, H.L., McLean, K., Sumner, D.J. et al. Absence of an effect of mianserin on the actions of clonidine or methyldopa in hypertensive patients. Eur J Clin Pharmacol 24, 15–19 (1983). https://doi.org/10.1007/BF00613921
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DOI: https://doi.org/10.1007/BF00613921