The subtype-selective alpha(2)-adrenoceptor antagonists BRL 44408 and ARC 239 also recognize 5-HT1A receptors in the rat brain

Several alpha(2)-adrenoceptor compounds have been reported to recognize 5-HT1A receptors. The interaction of the alpha(2A/D)- and alpha(2B/C)-adrenoceptor antagonists BRL 44408 (2-[2H-(1-methyl-1,3-dihydroisoindole) methyl]-4,5-dihydroimidazole) and ARC 239 (2-[2-[4-(o-methoxyphenyl)piperazin-1-yl] ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolinedione) with 5-HT1A receptors was evaluated in rat brain. Competition experiments in cortex with both compounds against the specific binding of the 5-HT1A receptor radioligand [H-3]8-OH-DPAT (8-hydroxy-2-(n-dipropyl-amine)-tetralin) yielded K-i values in the nanomolar range, fairly close to their previously reported affinities for alpha(2)-adrenoceptors. Similar K-i values were obtained under alpha(2)-adrenoceptor masking conditions by competition assays of these compounds against the alpha(2)-adrenoceptor and 5-HT1A receptor radioligand [H-3]RX 821002 (2-methoxy idazoxan) specific binding in hippocampus. The results indicate that BRL 44408 and ARC 239 recognize 5-HT1A receptors in addition to alpha(2)-adrenoceptors. The fact should be considered when using these compounds to study alpha(2)-adrenoceptor subtypes.