Summary
The purpose of the present study was to characterize the effects of mianserin at α2-adrenoceptors. Firstly, the action of mianserin on postganglionic sympathetic fibres has been studied using the tachycardia induced by stimulation of the cardiac nerve in dogs. Mianserin increased this tachycardia, but could not prevent the inhibitory effect of clonidine in this model. However, an antagonistic effect of mianserin against clonidine was observed when animals were pretreated with desipramine. Secondly, mianserin antagonized the inhibitory effect of clonidine on the electrically stimulated guinea-pig ileum. In high concentrations, mianserin reduced both electrically and acetylcholine induced contractions. Thirdly, mianserin antagonised the sleep induced by clonidine in chickens.
These results are consistent with α2-adrenoceptor blocking properties of mianserin in peripheral noradrenergic fibres in dogs, in cholinergic fibres in guinea-pig ileum and in the central nervous system in chickens.
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References
Andréjak M, Pommier Y, Mouillé P, Schmitt H (1980) Effect of some α-adrenoceptor agonists and antagonists on the guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 314:83–87
Baumann PA, Maître L (1975) Effects of mianserin on noradrenaline uptake and release. Naunyn-Schmiedeberg's Arch Pharmacol 287:R3
Baumann PA, Maître L (1977) Blockade of presynaptic α-receptors and of amine uptake in the rat brain by the antidepressants mianserin. Naunyn-Schmiedeberg's Arch Pharmacol 300:31–37
Borowski E, Ehrl H, Starke K (1976) Relative pre-and postsynaptic potencies of α-adrenolytic drugs. Naunyn-Schmiedeberg's Arch Pharmacol 293:R3
Cambridge D, Davey M (1980) Comparison of the α-adrenoceptors located on sympathetic and parasympathetic nerve terminals. Br J Pharmacol 69:345P
Cavero I, Roach AG (1978) The effect of prazosin on the clonidine induced hypotension and bradycardia in rats and sedation in chicks. Br J Pharmacol 62:468P-469P
Cavero I, Gomeni R, Lefèvre-Borg F, Roach AG (1979) Effects of mianserin on noradrenaline uptake, cardiac presynaptic and vascular postsynaptic α-adrenoceptors. Br J Pharmacol 66:132P-133P
Cavero I, Gomeni R, Lefèvre-Borg F, Roach AG (1980) Comparison of mianserin with desipramine, maprotiline and phentolamine on cardiac presynaptic and vascular postsynaptic α-adrenoceptors and noradrenaline uptake in pithed normotensive rats. Br J Pharmacol 68:321–332
Clineschmidt BV, Flataker LM, Faison E, Holmes R (1979) An in vivo model for investigation of α1-and α2-receptors in the C.N.S: studies with mianserin. Arch Int Pharmacodyn 242:59–76
Constantine JW, Weeks RA, McShane WK (1978) Prazosin and presynaptic α-receptors in the cardioaccelerator nerve of the dog. Eur J Pharmacol 50:51–60
Delbarre B, Schmitt H (1969) Influences pharmacologiques exercées sur la durée du sommeil provoqué chez le poussin par le 2-(2,6-dichlorophénylamino)-2-imidazoline hydrochloride (St 155, Catapresan). CR Soc Biol (Paris) 163:1922–1926
Delbarre B, Schmitt H (1971) Sedative effects of α-sympathomimetic drugs and their antagonism by adrenergic and cholinergic blocking drugs. Eur J Pharmacol 13:356–363
Delbarre B, Schmitt H (1973) A further attempt to characterize sedative receptors activated by clonidine in chickens and mice. Eur J Pharmacol 22:355–359
Docherty JR, McGrath JC (1980) An examination of factors influencing adrenergic transmission in the pithed rat, with special reference to noradrenaline uptake mechanism and post-junctional α-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 313:101–111
Doggrell SA (1980) Effect of mianserin on noradrenergic transmission in the rat anococcygeus muscle. Br J Pharmacol 68:241–250
Doxey JC, Everitt J, Metcalf G (1978) Mianserin. An analysis of its peripheral autonomic actions. Eur J Pharmacol 51:1–10
Drew GM (1978) Pharmacological characterization of the presynaptic α-adrenoceptors regulating cholinergic activity in the guinea-pig ileum. Br J Pharmacol 64:293–306
Gardner CR, Wilford AE (1980) The effects of mianserin, amitriptyline, ciclazindol and viloxazine on presynaptic α-receptors in isolated rat atria. Br J Pharmacol 68:184P-185P
Goodlet L, Sugrue MF (1974) The effect of a new antidepressant, ORG-GB94, on amine uptake mechanisms. Br J Pharmacol 52:431P
Harper B, Hughes IE (1977) 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 59:651–660
Harper B, Hughes IE (1979) Presynaptic α-adrenoceptor blocking properties among tri-and tetra-cyclic antidepressant drugs. Br J Pharmacol 67:511–517
Hoefke W, Kobinger W (1966) Pharmakologische Wirkungen des 2-(2,6-Dichlorophenylamino)-2 imidazolin-hydrochlorid einer neuen antihypertensiven Substanz. Arzneimittel Forsch 16:1038–1050
Langer SZ (1974) Presynaptic regulation on catecholamines release. Biochem Pharmacol 23:1793–1800
Mouillé P, Huchet AM, Lucet B, Chelly J, Schmitt H (1979) Interactions between clonidine and some α-adrenoceptor blocking drugs on the tachycardic response to stimulation of the cardiac nerve in dogs. J Cardiovasc Pharmacol 1:515–528
Paton WDM (1955) The response of the guinea-pig ileum to electrical stimulation by coaxial electrodes. J Physiol (Lond) 127:40–41
Paton WDM (1957) The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum. Br J Pharmacol 12:119–127
Raiteri IM, Angelini F, Bertollini A (1976) Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes. J Pharm Pharmacol 28:483–488
Roach AG, Lefèvre F, Cavero I (1978) Effects of prazosin and phentolamine on cardiac presynaptic α-adrenoceptors in the cat, dog and rat. Clin Exp Hypertension 1:87–101
Robson RD, Antonaccio MJ, Saelens JK, Liebman J (1978) Antagonism by mianserin and classical α-adrenoceptor blocking drugs of some cardiovascular and behavioral effects of clonidine. Eur J Pharmacol 47:431–442
Schmitt H (1977) The pharmacology of clonidine and related products. In: Gross F (ed) Antihypertensive agents. Handbook of Experimental Pharmacology. Springer Berlin Heidelberg New York, pp 300–396
Starke K (1977) Regulation of noradrenaline release by presynaptic receptor system. Rev Physiol Biochem Pharmacol 77:1–24
Starke K, Wagner J, Schumann HJ (1972) Adrenergic neuron blockade by clonidine: comparison with guanethidine and local anesthetics. Arch Int Pharmacodyn Ther 195:291–308
Sugrue MF (1980) The inability of chronic mianserin to block central α2-adrenoceptors. Eur J Pharmacol 68:377–380
Taube HD, Starke K, Borowski E (1977) Presynaptic receptor systems on the noradrenergic neurons of rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 299:123–141
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 histamine. Eur J Pharmacol 16:336–346
Werner V, Starke K, Schumann HJ (1972) Actions of clonidine and 2-(2-methyl-6-ethyl-cyclohexylamino)-2-oxazoline on postganglionic autonomic nerves. Arch Int Pharmacodyn 195:282–290
Wikberg J (1978) Differentiation between pre-and post-junctional α-receptors in guinea-pig ileum and rabbit aorta. Acta Physiol Scand 103:225–239
Yamaguchi I, Kopin I (1980) Differential inhibition of alpha-1 and alpha-2 adrenoceptor-mediated pressor response in pithed rats. J Pharmacol Exp Ther 214:275–281
Zaïmis E (1970) On the pharmacology of Catapres (St 155). In: Conolly ME (ed) Catapres in hypertension, Butterworths, London, pp 9–22
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Pommier, Y., Andréjak, M., Mouillé, P. et al. Interaction between mianserin and clonidine at α 2-Adrenoceptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 318, 288–294 (1982). https://doi.org/10.1007/BF00501167
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DOI: https://doi.org/10.1007/BF00501167