Paroxetine is the most potent and one of the most specific serotonin uptake inhibitors. High-affinity3H-paroxetine and3H-imipramine binding was compared in rat neuronal membranes.
TheKd value for3H-paroxetine binding to neuronal membranes was 0.08 nM, which is exactly the same value as with platelet membranes. TheKd value for3H-imipramine binding to neuronal membranes was about 4 nM, which is higher than theKd value for3H-imipramine binding to platelet membranes (0.5 nM).
The results indicated that the3H-paroxetine binding site is identical in neuronal membranes and in platelet membranes; this binding site is probably located on the serotonin transport mechanism. In addition, part of the highaffinity3H-imipramine binding to neuronal membranes is probably located on the serotonin transport mechanism, but another part is located elsewhere. Furthermore the polypeptides containing the3H-imipramine binding sites may not be identical in neuronal and platelet membranes.
3H-paroxetine 3H-imipramine Binding sites Rat neuronal membranes
Buus Lassen J, Lund J, Søndergaard I (1980) Central and peripheral 5-HT uptake in rats treated chronically with femoxetine, paroxetine and chlorimipramine. Psychopharmacology 68:229–233CrossRefGoogle Scholar
Fuxe K, Calza L, Benfenati F, Zini I, Agnati LF (1983) Quantitative autoradiographic localization of3H-imipramine binding sites in the brain of the rat: Relationship to ascending 5-hydroxytryptamine neuron systems. Neurobiology 80:3836–3840Google Scholar
Green JP, Maayani S (1977) Tricyclic antidepressant drugs block histamine H2 receptor in brain. Nature 269:163–165CrossRefPubMedGoogle Scholar
Hyttel J (1982) Citalopram pharmacological profile of a specific serotonin-uptake inhibitor with antidepressant activity. Prog Neuro-Psychopharmacol Biol Psychiatr 6: 277–295CrossRefGoogle Scholar
Langer SZ, Moret C, Raisman R, Dubocovich ML, Briley M (1980) High-affinity3H-imipramine binding in rat hypothalamus: Association with uptake of serotonin but not of norepinephrine. Science 210:1133–1135PubMedGoogle Scholar
Mellerup ET, Plenge P, Engelstoft M (1983) High affinity binding of3H-paroxetine and3H-imipramine to human platelet membranes. Eur J Pharmacol 96:303–309CrossRefPubMedGoogle Scholar
Mellerup ET, Plenge P, Nielsen M (1985) Size determination of binding polymers for3H-imipramine and3H-paroxetine in human platelet membranes. Eur J Pharmacol 106:411–413CrossRefGoogle Scholar
Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356CrossRefPubMedGoogle Scholar
Plenge P, Mellerup ET (1984) Imipramine binding site temperatur dependence of the binding of3H-labeled imipramine and3H-labeled paroxetine to human platelet membrane. Biochim Biophys Acta 770:22–28PubMedGoogle Scholar
Reith MEA, Sershen H, Allen D, Lathja A (1983) High-and low-affinity binding of3H-imipramine in mouse ccrebral cortex. J Neurochem 40:389PubMedGoogle Scholar
Sette M, Raisman R, Briley M, Langer SZ (1981) Localisation of tricyclic antidepressant binding sites on serotonin nerve terminals. J Neurochem 37:40–42PubMedGoogle Scholar
Snyder SH, Yamamura HL (1977) Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry 34:236–269PubMedGoogle Scholar
U'Prichard DC, Greenberg DA, Sheehan PP, Snyder SH (1978) Tricyclic antidepressants: Therapeutic properties and affinity for noradrenergic receptor binding sites in the brain. Science 199:197–198PubMedGoogle Scholar