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 [3H]8-OH-DPAT (8-hydroxy-2-(n-dipropyl-amine)-tetralin) yielded Ki values in the nanomolar range, fairly close to their previously reported affinities for alpha 2-adrenoceptors. Similar Ki 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 [3H]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.