Summary
A series of nitro derivatives of imipramine have been prepared by nitration of imipramine. Several of the products, especially 2-nitroimipramine (2) and 2,8-dinitroimipramine (4) were found to be very potent inhibitors of [3H] serotonin uptake and high affinity [3H] imipramine binding in human platelets. In contrast to the parent antidepressant, imipramine, the inhibition of platelet [3H] serotonin uptake and [3H] imipramine binding by the nitro derivatives of imipramine was long-acting and essentially irreversible at low temperatures. These compounds should prove to be valuable tools for subsequent studies on the purification and characterization of the transport protein(s) involved in serotonin uptake and may have novel behavioral and clinical effects.
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References
Briley MS, Raisman R, Langer SZ (1979) Human platelets possess high affinity binding sites for [3H] imipramine. Eur J Pharmacol 58:347–348
Carlsson A, Fuxe K, Ungerstedt U (1968) The effect of imipramine on central 5-hydroxytryptamine neurons. J Pharm Pharmacol 20:150–151
Costa JL, Murphy DL, Kafka MS (1977) Demonstration and evaluation of apparent cytoplasmic and vesicular serotonin compartments in human platelets. Biochem Pharmacol 26:517–521
Figge J, Leonard P, Richelson E (1979) Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum. Eur J Pharmacol 59:479–483
Glowinski J, Axelrod J (1964) Inhibition of uptake of tritiated noradrenaline in intact rat brain by imipramine and related compounds. Nature 204:1318–1319
Green JP, Maayani S (1977) Tricyclic antidepressant drugs block histamine H2 receptor in brain. Nature 269:163–165
Langer SZ, Moret C, Raisman R, Dubocovich ML, Briley M (1980) High affinity [3H] imipramine binding in rat hypothalamus: association with uptake of serotonin but not of norepinephrine. Science 210:1133–1135
Marshall EF, Stirling GS, Tait AC, Todrick A (1960) The effect of iproniazide and imipramine on the blood platelet 5-hydroxytryptamine level in man. Br J Pharmacol 15:35–41
Paul SM, Rehavi M, Skolnick P, Goodwin FK (1980) Demonstration of specific high affinity binding sites for [3H] imipramine on human platelets. Life Sci 26:953–959
Paul SM, Rehavi M, Rice KC, Ittah Y, Skolnick P (1981) Does high affinity [3H] imipramine binding label serotonin reuptake sites in brain and platelets. Life Sci 28:2753–2760
Peroutka SJ, Snyder SH (1980) Long term antidepressant treatment lowers spiroperidol-labeled serotonin receptors. Science 210:88–90
Raisman R, Briley MS, Langer SZ (1979) Specific tricyclic antidepressant binding sites in rat brain. Nature 281:148–150
Rehavi M, Maayani S, Sokolovsky M (1977) Tricyclic antidepressants as antimuscarinic drugs: in vivo and in vitro studies. Biochem Pharmacol 26:1559–1567
Rehavi M, Paul SM, Skolnick P, Goodwin FK (1980) Demonstration of specific high affinity binding sites for [3H] imipramine in human brain. Life Sci 26:2273–2279
Rehavi M, Ittah Y, Rice KC, Skolnick P, Goodwin FK, Paul SM (1981) 2-Nitroimipramine: a selective irreversible inhibitor of [3H] serotonin uptake and [3H] imipramine binding in platelets. Biochem Biophys Res Commun 99:954–959
Snyder SH, Yamamura HI (1977) Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry 34:236–239
U'Prichard DC, Greenberg DA, Sheehan PP, Snyder SH (1978) Tricyclic antidepressants: therapeutic properties and affinity for α-noradrenergic receptor binding sites in the brain. Science 199:197–198
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Rehavi, M., Ittah, Y., Skolnick, P. et al. Nitroimipramines — Synthesis and pharmacological effects of potent long-acting inhibitors of [3H] serotonin uptake and [3H] imipramine binding. Naunyn-Schmiedeberg's Arch. Pharmacol. 320, 45–49 (1982). https://doi.org/10.1007/BF00499070
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DOI: https://doi.org/10.1007/BF00499070