Effects of Iodoproxyfan, a Potent and Selective Histamine H3 Receptor Antagonist, on Alpha 2 and 5-HT3 Receptors

Overview

Journal Inflamm Res

Specialties Allergy & Immunology
Pathology

Date 1995 Jul 1

PMID 8564527

Citations 2

Authors

E Schlicker

H Pertz

H Bitschnau

K Purand

M Kathmann

S Elz

W Schunack

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Detection of multiple H3 receptor affinity states utilizing [3H]A-349821, a novel, selective, non-imidazole histamine H3 receptor inverse agonist radioligand.

Witte D, Yao B, Miller T, Carr T, Cassar S, Sharma R Br J Pharmacol. 2006; 148(5):657-70.

PMID: 16715122 PMC: 1751875. DOI: 10.1038/sj.bjp.0706752.

Potencies of antagonists chemically related to iodoproxyfan at histamine H3 receptors in mouse brain cortex and guinea-pig ileum: evidence for H3 receptor heterogeneity?.

Schlicker E, Kathmann M, Bitschnau H, Marr I, Reidemeister S, Stark H Naunyn Schmiedebergs Arch Pharmacol. 1996; 353(5):482-8.

PMID: 8740140 DOI: 10.1007/BF00169166.

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