Abstract
Studies examining the interaction of various radiolabeled psychotropic agents with neuronal membranes have played an important role in elucidating the central sites of action of many of these compounds. The benzodiazepines and opiate alkaloids, for example, have been demonstrated to interact with a high degree of specificity at recognition sites on neuronal membranes following pharmacologically relevant doses. In contrast, antidepressants interact with many membrane sites with varying degrees of specificity and affinity, including both pre- (Koe, 1976) and postsynaptic (Snyder and Yamamura, 1977) re-uptake and/or receptor sites, and perhaps other, as yet unidentified, binding or recognition sites (Biegon and Samuel, 1979). Therefore, the in vitro conditions employed in studying the binding of radiolabeled antidepressants should be clearly defined and optimized for selective and specific ‘labeling’ of a given membrane site. In this report, we will review studies from our laboratories on the binding of [3H]-imipramine and [3H]-desipramine to membrane preparations from rat and human brain as well as platelets, emphasizing the conditions under which these ligands will selectively label the serotonin and norepinephrine transport sites, respectively.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Biegon, A. and Samuel, D. (1979). Binding of labeled antidepressants to rat brain tissue. Biochem. Pharmacol., 28, 3361–6
Briley, M.S., Langer, S.Z., Raisman, R., Sechter, D. and Zarifian, E. (1980). Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients. Science, 209, 303–5
Koe, B.K. (1976). Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat cortex. J. Pharmacol. Exp. Ther., 199, 649–61
Laduron, P.M., Robbyns, M. and Schotte, A. (1982). [3H]Desipramine and [3H]imipramine binding are not associated with noradrenaline and serotonin uptake in brain. Eur. J. Pharmacol., 78, 491–3
Langer, S.Z., Moret, C., Raisman, R., Dubocovich, M.L. and Briley, M. (1980a). High affinity [3H]imipramine binding in rat hypothalamus: association with uptake of serotonin but not of norepinephrine. Science, 210, 1133–5
Langer, S.Z., Raisman, R. and Briley, M. (1980b). Stereoselective inhibition of [3H] imipramine binding by antidepressant drugs and their derivatives. Eur. J. Pharmacol., 64, 89–90
Langer, S.Z., Raisman, R. and Briley, M. (1981). High affinity [3H]DMI binding is associated with neuronal noradrenaline uptake in the periphery and central nervous system. Eur. J. Pharmacol., 72, 423–4
Lee, C.H. and Snyder, S.H. (1981). Norepinephrine neuronal uptake sites in rat brain membranes labeled with [3H]desipramine. Proc. Natl. Acad. Sci., 78, 4250–6
Paul, S.M., Rehavi, M., Rice, K.C., Ittah, Y. and Skolnick, P. (1981a). Does high affinity [3H]imipramine binding label serotonin reuptake sites in brain and platelet? Life Sci., 28, 2753–60
Paul, S.M., Rehavi, M., Skolnick, P., Ballenger, J.C. and Goodwin, F.K. (1981b). Depressed patients have decreased binding of tritiated imipramine to platelet serotonin ‘transporter’. Arch. Gen. Psychiatry, 38, 1315–17
Paul, S.M., Rehavi, M., Skolnick, P. and Goodwin, F.K. (1980). Demonstration of specific high affinity binding sites for [3H]imipramine on human platelets. Life Sci., 26, 953–9
Raisman, R., Briley, M. and Langer, S.Z. (1979). Specific tricyclic antidepressant binding sites in rat brain. Nature, 281, 148–50
Rehavi, M., Ittah, Y., Rice, K.C., Skolnick, P., Goodwin, F.K. and Paul, S.M. (1981a). 2-Nitroimipramine: a selective irreversible inhibitor of [3H]serotonin uptake and [3H]imipramine binding in platelets. Biochem. Biophys. Res. Comm., 99, 954–9
Rehavi, M., Paul, S.M., Skolnick, P. and Goodwin, F.K. (1980). Demonstration of specific high affinity binding sites for [3H]imipramine in human brain. Life Sci., 26, 2273–9
Rehavi, M., Skolnick, P., Brownstein, M.J. and Paul, S.M. (1982a). High affinity binding of [3H] desipramine to rat brain: a presynaptic marker for noradrenergic uptake sites. J. Neurochem., 38, 889–95
Rehavi, M., Skolnick, P., Hulihan, B. and Paul, S.M. (1981b). High affinity binding of [3H]desipramine to rat cerebral cortex: relationship to tricyclic antidepressant-induced inhibition of norepinephrine uptake. Eur. J. Pharmacol., 70, 597–9
Rehavi, M., Skolnick, P. and Paul, S.M. (1982b). Solubilization and partial purification of the high affinity [3H] imipramine binding site from human platelets. FEBS Lett., 150 (2), 514–18
Rehavi, M., Skolnick, P. and Paul, S.M. (1983). Subcellular distribution of high affinity [3H] imipramine binding and [3H] serotonin uptake in rat brain. Eur. J. Pharmacol., in press
Snyder, S.H. and Yamamura, H.I. (1977). Antidepressants and the muscarinic acetylcholine receptor. Arch. Gen. Psychiatry, 34, 236–9
Whittaker, V. and Barker, L. (1972). The subcellular fractionation of brain tissue with special reference to the preparation of synaptosomes and their component organelles. In Methods of Neurochemistry, vol. 2 (ed. R. Fried), Marcel Dekker, New York, pp. 1–52
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Copyright information
© 1983 The contributors
About this chapter
Cite this chapter
Rehavi, M., Skolnick, P., Paul, S.M. (1983). Characterization of high-affinity antidepressant binding to rat and human brain. In: Gram, L.F., Usdin, E., Dahl, S.G., Kragh-Sørensen, P., Sjöqvist, F., Morselli, P.L. (eds) Clinical Pharmacology in Psychiatry. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-06671-1_30
Download citation
DOI: https://doi.org/10.1007/978-1-349-06671-1_30
Publisher Name: Palgrave Macmillan, London
Print ISBN: 978-1-349-06673-5
Online ISBN: 978-1-349-06671-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)