1 Dopamine D2-receptors were solubilized from synaptosomal membranes of the bovine caudate nucleus using different detergents.

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Several ergot alkaloid derivatives have been tested for their ability to inhibit receptor binding of [³H]spiperone (D₂ dopamine receptors) and [³H]dopamine (D₃ dopamine receptors) in the bovine caudate nucleus. Dopaminergic activity was correlated to their chemical structure. The potencies of ergot alkaloids for displacing [³H]spiperone binding can be ranked in the following order: lisuride > ergosine > bromodihydroergosine > bromoergosine ∼ dihydroergosine ∼ ergosinine ∼ dihydroergocryptine > bromoergocryptine > CH-29 717 > saccharinoergosinine = saccharinoergosine > dihydroergosinine. The potencies of these compounds for displacing [3H]dopamine binding can be ranked in the following order: lisuride > ergosinine ∼ ergosine > dihydroergosine > bromodihydroergosine ∼ CH-29 717 – bromoergocryptine ∼ bromoergosine ∼ dihydroergocryptine > saccharinoergosine, saccharinoergosinine, dihydroergosinine. Displacement of both radioligands was unaffected by GTP. Binding characteristics of ergot alkaloids examined revealed antagonist-like properties of binding to D₂ and agonist-like properties of binding to D3 receptors. Introduction of bromine into position 2, selective hydrogenation of 9,10-dihydroderivatives, or isomerization in position 8 of the ergot alkaloid molecule did not drastically change binding parameters of these compounds. However, an alpha-configuration in position 8 combined with hydrogenation of the delta-9,10-double bond of dihydroergosinine, significantly decreased its affinity to both D₂ and D₃ receptors in comparison with dihydroergosine or ergosinine, suggesting stereoselectivity of dopamine receptors towards the pair dihydroergosine/dihydroergosinine.

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