Summary
The antimuscarinic activity of amitriptyline, desipramine, iprindole, mianserin and viloxazine on prejunctional sympathetic nerve endings were compared in the isolated rabbit ear artery. In the presence of cocaine (10 μM) and yohimbine (1 μM), amitriptyline (0.5–1 μM), desipramine (1–3 μM) and iprindole (5–10 μM), desipramine (1–3 μM) and iprindole (5–10 μM) produced parallel rightward shifts of the concentration-response curve for the inhibitory effect of carbachol (CCh) on responses to electrical stimulation of the preparation at 3 Hz. Mianserin (3 μM) produced some inhibition but altered the slope of the concentration-responses curve to CCh while viloxazine (≤10 μM) produced no inhibition.
The depression of tritium efflux by CCh from arteries preincubated in 3H-noradrenaline was inhibited significantly (P<0.05) by amitriptyline (0.1 μM) and desipramine (1 μM) and not by iprindole (17 μM), mianserin (3 μM) or viloxazine (10 μM). Amitriptyline was 10-fold more active than desipramine and at least 30-fold more active than the other antidepressants as a muscarine receptor blocking drug in this preparation.
Thus, mianserin, viloxazine and iprindole exhibit much weaker antimuscarinic activity relative to amitriptyline on prejunctional muscarine receptors on sympathetic nerve endings compared with that observed by others for excitatory muscarine receptors in sympathetic ganglia. The findings support an earlier suggestion that these receptors differ.
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References
Allen GS, Rand MJ, Story DF (1973) Techniques for studying adrenergic transmitter release in an isolated perfused artery. Cardiovasc Res 7:423–428
Atkinson J, Ladinsky H (1972) A quantitative study of the anticholinergic action of several tricyclic antidepressants on the rat isolated fundal strip. Br J Pharmacol 45:519–524
Bassett JR, Cairncross KD, Hacket NB, Story M (1969) Studies on the peripheral pharmacology of fenazoxine, a potential antidepressant. Br J Pharmacol 37:69–78
Brown DA, Forward A, Marsh S (1980a) Antagonist discrimination between ganglionic and ileal muscarinic receptors. Br J Pharmacol 71:362–364
Brown J, Doxey JC, Handley S (1980b) Effects of α-adrenoceptor agonists and antagonists and of antidepressant drugs on pre- and postsynaptic α-adrenoceptors. Eur J Pharmacol 67:33–40
De la Lande IS, Rand MJ (1965) A simple isolated nerve-blood vessel preparation. Aust J Exp Biol Med Sci 43:639–656
Dubocovich ML, Langer SZ, Massingham R (1980) Lack of correlation between presynaptic inhibition of noradrenaline release and end-organ responses during nerve stimulation. Br J Pharmacol 69:81–90
Fozard JR, Muscholl E (1972) Effects of several muscarinic agonists on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart. Br J Pharmacol 45:616–629
Frankhuyzen AL, Bonta IL (1974) Effect of mianserin, a potent antiserotonin agent, on the isolated rat stomach fundus preparation. Eur J Pharmacol 25:40–50
Fuder H, Meiser C, Wormstall H, Muscholl E (1981) The effects of several muscarinic antagonists on pre- and post-synaptic receptors in the isolated rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 316:31–37
Glover A (1973) In: Burrows GD (ed) Handbook of studies on depression, Chapter 8. Modes of action of antidepressants by M. J. Rand & M. W. McCulloch, Excerpta Med Amsterdam 1977, pp 137–155
Golds PR, Przyslo FR, Strange PG (1980) The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol 68:541–549
Gollis MG, Shepherd JT (1980) Interaction of the tricyclic antide-pressant, amitriptyline, with prejunctional alpha and muscarinic receptors in the dog saphenous vein. J Pharmacol Exp Ther 213:616–622
Greenwood DT (1975) Animal pharmacology of viloxazine (Vivalan). J Int Med Res 3 (Suppl. 3):18–30
Jaramillo J, Volle RL (1967) Ganglion blockade by muscarine, oxotremorine and AHR-602. J Pharmacol Exp Ther 158:80–88
Jones RSG (1980) Long-termed administration of atropine, imipramine and viloxazine alters responsiveness of rat cortical neurones to acetylcholine. Can J Physiol Pharmacol 58:531–535
Kopera H (1978) Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo. Br J Clin Pharmacol 5:29S-34S
Kwok YH, Mitchelson F (1981) Comparison of the antimuscarinic activity of mianserin and amitriptyline in the cat superior cervical ganglion. Naunyn-Schmiedeberg's Arch Pharmacol 316:161–164
Kwok YH, Mitchelson F (1982) The effect of amitriptyline, mianserin and viloxazine at pre- and post-junctional muscarinic receptors in guinea-pig ileal longitudinal muscle. Canad J Physiol Pharmacol 60: 193–200
Langer SZ (1970) The metabolism of (3H)-noradrenaline released by electrical stimulation from the isolated nictitating membrane of the cat and from the vas deferens of the rat. J Physiol (Lond) 208:515–546
Li CK, Mitchelson F (1980) The selective antimuscarinic action of stercuronium. Br J Pharmacol 70:313–321
McCulloch MW, Story DF (1972) Antagonism of noradrenaline and histamine by desipramine in the isolated artery of the rabbit ear. Br J Pharmacol 46:140–150
McEwen LM (1956) The effect on the rabbit heart of vagal stimulation and its modification by cocaine, hexamethonium and ouabain. J Physiol (Lond) 131:678–689
Pinder RM, Brogden RN, Speight TM, Avery GS (1977) Viloxazine: A review of its pharmacological properties and therapeutic efficacy in depressive illness. Drugs 13:401–421
Rand MJ, Varma B (1970) The effects of cholinomimetic drugs on responses to sympathetic nerve stimulation and noradrenaline in the rabbit ear artery. Br J Pharmacol 38:758–770
Schrold J, Nedergaard OA (1977) Neuronal and extraneuronal outflow of (3H)-noradrenaline induced by electrical field stimulation of an isolated blood vessel. Acta Physiol Scand 101:129–143
Shein K, Smith SE (1978) Structure activity relationships for the anticholinoceptor action of tricyclic antidepressants. Br J Pharmacol 62:567–571
Starke K, Borowski E, Endo T (1975) Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Eur J Pharmacol 34:385–388
Steinsland DS, Furchgott RF (1975) Vasoconstriction of the isolated rabbit ear artery caused by nicotinic agonists acting on adrenergic neurons. J Pharmacol Exp Ther 193:128–137
Steinsland DS, Furchgott RF, Kirpekar SM (1973) Inhibition of adrenergic neurotransmission by parasympathomimetics in the rabbit ear artery. J Pharmacol Exp Ther 184:346–356
Story DF, Story ME, McCulloch MW, Hope W, Rand MJ (1974) Effects of tricyclic antidepressants on uptake and release of 3H-noradrenaline in isolated guinea-pig atria. Clin Exp Pharmacol Physiol 1:429–439
Weinstock M, Cohen D (1976) Tricyclic antidepressant drugs as antagonists of muscarinic receptors in sympathetic ganglia. Eur J Pharmacol 40:321–328
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Kwok, Y.H., Mitchelson, F. The effect of some antidepressants on prejunctional muscarinic receptors on the sympathetic nerves of the isolated rabbit ear artery. Naunyn-Schmiedeberg's Arch. Pharmacol. 320, 14–19 (1982). https://doi.org/10.1007/BF00499065
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DOI: https://doi.org/10.1007/BF00499065