title: Antagonism of pre and postsynaptic alpha-adrenoreceptors by BE 2254 (HEAT) and prazosin.
abstract: 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.
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D044024:Tetralones
chemical_list: D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D011799:Quinazolines; D013764:Tetrahydronaphthalenes; D044024:Tetralones; C010652:BE 2254; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; D011224:Prazosin