Preferential blockade of postsynaptic alpha-adrenoceptors by BE 2254.
The effects of 2-[beta-(4-hydroxyphenyl)-ethyl-aminomethyl]-tetralone (BE 2254) on pre- and postsynaptic alpha-adrenoceptors were studies in isolated rabbit hearts and strips of rabbit pulmonary arteries. The KCl (80 mM)-evoked output of endogenous noradrenaline from perfused hearts was significantly increased by BE 2254 (10(-7)-10(-6) M). The inhibitory effect of clonidine (10(-7) M) on KCl-evoked noradrenaline output was antagonized by BE 2254 (10(-6) and 10(-5) M) indicating that the compound causes a blockade of presynaptic alpha-adrenoceptors. In superfused pulmonary arteries, BE 2254 produced a parallel shift to the right of the concentration-response curve for noradrenaline: increasing effect on tension, pA2 = 8.75. The electrically (2 Hz) evoked 3H overflow from arteries preincubated with 3H-noradrenaline was increased by BE 2254 (3.2 x 10(-8)-3.2 x 10(-7) M). Considerably lower concentrations were sufficient to cause an inhibition of the electrically evoked increase in tension: 3.2 x 10(-9) M BE 2254 caused a 45% decrease. These results suggest that BE 2254, in spite of its rather high affinity to presynaptic alpha-adrenoceptors, preferentially blocks postsynaptic alpha-adrenoceptors.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000378:metabolism; D011817:Rabbits; D013569:Synapses / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D044024:Tetralones
D000317:Adrenergic alpha-Antagonists; D009281:Naphthalenes; D010627:Phenethylamines; D013764:Tetrahydronaphthalenes; D044024:Tetralones; C010652:BE 2254; D011189:Potassium Chloride; D003000:Clonidine; D009638:Norepinephrine