Antagonism of pre and postsynaptic alpha-adrenoreceptors by BE 2254 (HEAT) and prazosin.

1 The alpha-adrenoreceptor blocking effects of BE 2254 and prazosin have been studied in the pithed rat and guinea-pig ileum preparations. 2 BE 2254 was a competitive and potent antagonist of NA, Phenylephrine (PE) or stimulation-induced vasoconstriction in the pithed rat, but only exerted a weak antagonism of postsynaptic alpha 2-adrenoreceptor vasoconstriction induced by N,N-diMe-6,7-diOHATN (TL 99) or azepexole (BHT 933). The potency of BE 2254 against NA-induced vasoconstriction was markedly reduced by pretreatment with prazosin and propranolol. The antagonist effects of BE 2254 against TL 99-induced vasoconstriction was not altered by these pretreatments. Prazosin was without effect at postsynaptic alpha 2-adrenoreceptors. Neither antagonist blocked the pressor responses to angiotensin II (A II) nor the tachycardia-induced by exogenous NA, indicating specificity for alpha 2-adrenoreceptors. 3 BE 2254 was a potent antagonist of TL99-induced cardioinhibition (presynaptic alpha 2-adrenoreceptor effects) in the pithed rat, but may not act as a competitive antagonist in this preparation. Prazosin was without antagonist effect in this preparation. 4 In the transmurally stimulated guinea-pig ileum, BE 2254 was a potent antagonist of TL99, or clonidine-induced inhibition of the twitch response (presynaptic alpha 2-adrenoreceptor effects), but did not antagonize the effects of morphine. Prazosin was again without effect. 5 It was concluded that BE 2254 is a potent antagonist at presynaptic alpha 2-adrenoreceptors in vitro and in vivo, and at postsynaptic alpha 1-adrenoreceptors in vivo, but has only weak activity at vascular postsynaptic alpha 2-adrenoreceptors in the pithed rat. The differences in potency of BE 2254 in the pithed rat at pre- and postsynaptic alpha 2-adrenoreceptors suggests that these alpha-adrenoreceptor sub-types may differ.