Idazoxan (RX 781094) selectively antagonizes alpha 2-adrenoceptors on rat central neurons.

We have studied the alpha-adrenoceptor antagonist effects of idazoxan (RX 781094) in extracellular recordings from single locus coeruleus and dorsal raphe neurons of chloral hydrate-anesthetized rats. Idazoxan blocked alpha 2 responses with an ED50 of 14 +/- 8 micrograms/kg i.v., while the potency at alpha 1-receptors was only 420 +/- 190 micrograms/kg. A similar alpha 2 selectivity was seen when idazoxan was applied microiontophoretically. Idazoxan at doses which blocked alpha 1-receptors had little or no effect on locus coeruleus responses to morphine or dorsal raphe responses to LSD. When sodium pentobarbital was used as the anesthetic, systemically administered idazoxan slowed the firing rate of locus coeruleus cells, but iontophoretic experiments showed this to be an interaction with the anesthetic and not a direct agonist effect. We conclude that in rat brain idazoxan is a pure antagonist and that it has a selectivity for alpha 2- over alpha 1-receptors markedly superior to piperoxane, yohimbine, or rauwolscine.