tropisetron and iodoproxyfan

We determined the affinity and/or potency of the novel H3 receptor antagonist iodoproxyfan at alpha 2 and 5-HT3 receptors. Iodoproxyfan and rauwolscine (a reference alpha 2 ligand) (i) monophasically displaced 3H-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 with 3H-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 6.3 mumol/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 at alpha 2 receptors by at least 1.5 log units and that at 5-HT3 receptors by at least 3 log units.

Topics: Animals; Binding, Competitive; Cerebral Cortex; Dose-Response Relationship, Drug; Female; Guinea Pigs; Histamine H2 Antagonists; Ileum; Imidazoles; Indoles; Iodine Radioisotopes; Male; Mice; Muscle Contraction; Muscle, Smooth; Norepinephrine; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2; Receptors, Histamine H3; Reference Standards; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Tropisetron; Yohimbine