Subclasses of histamine H₃ antagonist binding sites in rat brain

Histamine H₃ antagonists have been reported to discriminate subclasses of histamine H₃ agonist binding in rat cortical membranes. This phenomenon was investigated by autoradiography of cryostat sections of rat forebrain labelled with [³H]N^α- methylhistamine ([³H]NAHM, 4 nM). Displacement curves with thioperamide detected a single site in cortex and striatum (pIC₅₀ 8.18±0.03). However, Hill coefficients (n_H 0.51±0.12) suggested the possible presence of multiple binding sites. Displacement with burimamide was consistent with two site models in all brain regions examined (pIC₅₀(A) 7.9±1.5; pIC₅₀(B) 5.6±0.7), except for the medial septum where a single site was detected. Elsewhere, the relative abundance of the two sites displaced by burimamide (H_3A: H_3B) appeared to be 1:2. Thioperamide may have failed to discriminate two sites because the IC₅₀s were too similar to be distinguished in the present autoradiographic study.