AUTORADIOGRAPHIC MAPPING OF 5-HT1B AND 5-HT1D RECEPTORS IN HUMAN BRAIN USING [H-3]ALNIDITAN, A NEW RADIOLIGAND

[H-3]alniditan, a new potent non-indole serotonin 5-HT1B/1D agonist, w as used as a radioligand to characterize 5-HT1B and 5-HT1D receptor (p reviously termed 5-HT1D beta and 5-HT1D alpha) in various regions of t he human brain. Quantitative receptor autoradiography was applied for high anatomical resolution and sensitivity. Highest densities of 5-HT1 B/1D receptors were found in the substantia nigra and in the globus pa llidus. High to moderate densities were measured in the caudate nucleu s, putamen, nucleus accumbens, central gray and hippocampal formation. Very low densities were detected in various cortical regions. In the cerebellum no [H-3]alniditan binding was detected. Selective 5-HT1B re ceptor labeling was achieved using [3H]alniditan in the presence of 30 0 nM of ketanserin (sufficient to block 5-HT1D receptor labeling). The identity of the 5-HT1B binding sites under these conditions was corro borated by the pIC(50) of sumatriptan, which corresponded to its affin ity for cloned human 5-HT1B receptors expressed in cells. Surprisingly , the distribution of selective 5-HT1B receptor labeling was completel y identical to the distribution of labeling of 5-HT1B + 5-HT1D recepto rs. The present data indicate that [H-3]alniditan is a suitable radiol igand for measuring 5-HT1B/1D receptor in the human brain and that the 5-HT1B binding sites are predominant in the presently investigated re gions of the human brain.