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Effects of iodoproxyfan, a potent and selective histamine H3 receptor antagonist, onα 2 and 5-HT3 receptors

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Abstract

We determined the affinity and/or potency of the novel H3 receptor antagonist iodoproxyfan atα 2 and 5-HT3 receptors. Iodoproxyfan and rauwolscine (a referenceα 2 ligand) (i) monophasically displaced3H-rauwolscine binding to rat brain cortex membranes (pKi 6.79 and 8.59); (ii) facilitated the electrically evoked tritium overflow from superfused mouse brain cortex slices preincubated with3H-noradrenaline (pEC50 6.46 and 7.91) and (iii) produced rightward shifts of the concentration-response curve (CRC) of (unlabelled) noradrenaline for its inhibitory effect on the evoked overflow (pA2 6.65 and 7.88). In the guinea-pig ileum, iodoproxyfan 6.3µmol/l failed to evoke a contraction by itself but depressed the maximum of the CRC of 5-hydroxytryptamine (pD′2 5.24). Tropisetron (a reference 5-HT3 antagonist) produced rightward shifts of the CRC of 5-hydroxytryptamine (pA2 7.84). In conclusion, the affinity/potency of iodoproxyfan at H3 receptors (range 8.3-9.7 [1]) exceeds that atα 2 receptors by at least 1.5 log units and that at 5-HT3 receptors by at least 3 log units.

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität Bonn, Reuterstrasse 2b, D-53113, Bonn, Germany

    E. Schlicker, H. Bitschnau & M. Kathmann

  2. Fachbereich Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2 und 4, D-14195, Berlin, Germany

    H. Pertz, K. Purand, S. Elz & W. Schunack

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  1. E. Schlicker
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  2. H. Pertz
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  3. H. Bitschnau
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  4. K. Purand
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  5. M. Kathmann
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  6. S. Elz
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  7. W. Schunack
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Schlicker, E., Pertz, H., Bitschnau, H. et al. Effects of iodoproxyfan, a potent and selective histamine H3 receptor antagonist, onα 2 and 5-HT3 receptors. Inflamm Res 44, 296–300 (1995). https://doi.org/10.1007/BF02032572

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