Vohra M M, Chaudhry A
Can J Physiol Pharmacol. 1984 Sep;62(9):1147-51. doi: 10.1139/y84-192.
The actions of benextramine, which blocks postjunctional alpha-adrenoceptors noncompetitively and irreversibly (non-equilibrium type) on prejunctional alpha-adrenoceptors (alpha 2) and postjunctional histamine H2 receptors, were studied in the mouse vas deferens, using clonidine and histamine, respectively, as the agonists. Both agonists caused a dose-related inhibition of the electrically evoked twitch responses, an inhibition that their respective antagonists (yohimbine or phentolamine, and cimetidine) antagonized competitively. Benextramine, however, antagonized the agonists' inhibitory effect noncompetitively. At the concentrations used, while clonidine or yohimbine and phentolamine protected the prejunctional alpha-adrenoceptors (alpha 2) against the benextramine noncompetitive blockade, histamine or cimetidine failed to protect the histamine H2 receptor against benextramine blockade. Therefore, although benextramine acts prejunctionally to block the alpha 2-adrenoceptors in the mouse vas deferens either by interacting directly with the same site as clonidine or yohimbine and phentolamine, or allosterically with a site close to it, it does not appear to act irreversibly, either directly or allosterically, with the same site as histamine or cimetidine. The mechanism by which benextramine blocks the histamine-induced inhibition of the electrically evoked twitch response in the mouse vas deferens remains to be established.
在小鼠输精管中，分别使用可乐定和组胺作为激动剂，研究了苄非他明的作用。苄非他明可非竞争性且不可逆地（非平衡型）阻断节后α-肾上腺素能受体（α2）和节后组胺H2受体。两种激动剂均引起电诱发抽搐反应的剂量相关抑制，这种抑制可被它们各自的拮抗剂（育亨宾或酚妥拉明，以及西咪替丁）竞争性拮抗。然而，苄非他明非竞争性地拮抗激动剂的抑制作用。在所使用的浓度下，虽然可乐定或育亨宾以及酚妥拉明可保护节前α-肾上腺素能受体（α2）免受苄非他明的非竞争性阻断，但组胺或西咪替丁未能保护组胺H2受体免受苄非他明的阻断。因此，尽管苄非他明在节前起作用，通过直接与可乐定或育亨宾以及酚妥拉明相同的位点相互作用，或与靠近该位点的别构位点相互作用来阻断小鼠输精管中的α2-肾上腺素能受体，但它似乎不会直接或别构地与组胺或西咪替丁相同的位点发生不可逆作用。苄非他明阻断组胺诱导的小鼠输精管电诱发抽搐反应抑制的机制仍有待确定。
