Abstract
Tricyclic antidepressants and monoamine oxidase inhibitors are presumed to act rapidly to elevate synaptic levels of norepinephrine (NE) and serotonin (5-HT) by inhibiting uptake and metabolism, respectively. Synaptic levels of NE, how-ever, are not controlled entirely by reuptake and metabolic processes, but are under the additional influence of a negative feedback inhibition mediated by an agonist action of NE itself upon α2-adrenoceptors located presynaptically on the noradrenergic nerve terminal (Timmermans and van Zwieten 1982). Antagonism of these so-called autoreceptors leads to enhancement of the release of NE from its storage sites in the nerve terminal and thereby to a situation akin to that following uptake inhibition. α2-Autoreceptors have been demonstrated to exist at almost all noradrenergic axons where postsynaptic α-adrenoceptors are known to occur, and they are widely distributed in the brain, particularly in the cortex. The possibility that α2-autoreceptor antagonism might lead to antidepressant properties has stimulated the development of a number of putative therapeutic agents, which vary widely in their potency and selectivity (Pinder 1985 a, b).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Baumann PA, Maitre L (1977) Blockade of the presynaptic a-receptors and of amine uptake in the rat brain by the antidepressant mianserin. Naunyn-Schmiedebergs Arch Pharmacol 300: 31–37
Cerrito F, Raiteri M (1981) Supersensitivity of central noradrenergic presynaptic autoreceptors following chronic treatment with the antidepressant mianserin. Eur J Pharmacol 70: 425–426
Charney DS, Heninger GR, Sternberg DE (1984) The effect of mianserin on α2-adrenergic receptor function in depressed patients. Br J Psychiatry 144: 407–416
Checkley SA, Glass IB, Shaw E (1982) Central α2-adrenoceptor function in depression. Lancet 1: 1359
Crossley DI (1984) The effects of idazoxan, an α2-adrenoceptor antagonist in depression — a preliminary investigation. Abstract of the 9th IUPHAR congress, London, 1984 (Abstract 1724P)
Elliott JM (1984) Platelet receptor binding studies in affective disorders. J Affective Disord 6: 219–239
Elliott HL, McLean K, Sumner DJ, Reid JL (1983) Absence of an effect of mianserin on the action of elonidine or methyldopa in hypertensive patients. Eur J Clin Pharmacol 24: 15–19
Nickolson VJ, Wieringa JH (1981) Presynaptic a-block and inhibition of noradrenaline and 5-hydroxytryptamine reuptake by a series of compounds related to mianserin. J Pharm Pharmacol 33: 760–766
Pinder RM (1983) Antidepressants and a-adrenoceptors. In: Gram LF, Usdin E, Dahl SG, Kragh-Sørensen P, Sjöqvist F, Morselli PL (eds) Clinical pharmacology in psychiatry: bridging the experimental-therapeutic gap. MacMillan, London, pp 268–287
Pinder RM ( 1985 a) Antidepressant drugs of the future. In: Iversen SE (ed) Psychopharmacology: recent advances and future prospects. Oxford University Press, London, pp 44–62
Pinder RM (1985 b) α2-Adrenoceptor antagonists as antidepressants. Drugs of the Future 10:841–857
Pinder RM (1985 c) Adrenoceptor interactions of the enantiomers and metabolites of mianserin. Are they responsible for the antidepressant effect? Acta Psychiatr Scand 72 [Suppl 320]: 1–9
Timmermans PBMWM, van Zwieten PA (1982) α-Adrenoceptors. Classification, localisation, mechanisms and targets for drugs. J Med Chem 25: 1389–1401
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Pinder, R.M., Sitsen, J.M.A. (1987). α2-Adrenoceptor Antagonists as Antidepressants: The Search for Selectivity. In: Dahl, S.G., Gram, L.F., Paul, S.M., Potter, W.Z. (eds) Clinical Pharmacology in Psychiatry. Psychopharmacology Series, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71288-3_13
Download citation
DOI: https://doi.org/10.1007/978-3-642-71288-3_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-71290-6
Online ISBN: 978-3-642-71288-3
eBook Packages: Springer Book Archive