[125I]Iodobolpyramine, a highly sensitive probe for histamine H1-receptors in guinea-pig brain

[125I]Iodobolpyramine is a novel 125I-ligand for histamine H1-receptors, synthesised using the 125I-Bolton Hunter reagent (2000 Ci/mmol) for acylation of an aminopentyl analogue of mepyramine. Its specific binding varied linearly with the concentration of guinea-pig cerebellar membranes and represented about 80% of the total. Selective interaction with H1-receptors was demonstrated by estimation of Ki values of known agonists and antagonists and confirmed by the low affinity of histamine H2- and H3-receptor antagonists and of non-histaminergic agents. At 25 degrees C, [125I]iodobolpyramine exhibited a slow association rate (180-240 min to reach equilibrium) and a slow dissociation rate (t1/2 = 201 min). Kinetic and saturation data yielded KD values of 0.05 and 0.15 nM, respectively, indicating that it is among the most potent H1-receptor antagonists known. The sensitivity for detecting H1-receptors in guinea-pig cerebellum using [125I]iodobolpyramine was increased 50-fold relative to use of [3H]mepyramine. Well-contrasted autoradiograms of guinea-pig brain, obtained after a short exposure time, confirmed previous H1-receptor localisation established with [3H]mepyramine and revealed new localisations, e.g. in cerebral cortex and nucleus accumbens.