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.
Department of Pharmacology, University of the Basque Country, Leioa, Bizkaia, Spain. memaj@lg.ehu.es
J J
JJ
Meana
L F
LF
Callado
A
A
Pazos
B
B
Grijalba
J A
JA
García-Sevilla
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D007546:Isoquinolines; D010879:Piperazines; D011985:Receptors, Serotonin; C032994:AR-C239; C072125:BRL 44408