Finberg J P, Tal A
Br J Pharmacol. 1985 Mar;84(3):609-17. doi: 10.1111/j.1476-5381.1985.tb16140.x.
Responses of the isolated vas deferens of the rat to clonidine (inhibition of contractions to field stimulation at 0.1 Hz) and noradrenaline (contraction of longitudinal muscle) were determined after one or 21 daily injections of the animals with desmethylimipramine, clorgyline, selegiline or tranylcypromine. Desmethylimipramine (10 mg kg-1) and clorgyline (2 mg kg-1) increased the clonidine EC50 in the isolated vas deferens after 21 but not after one daily injection(s). Tranylcypromine (5 mg kg-1) increased clonidine EC50 after both one and 21 injections and selegiline (1 mg kg-1) did not affect clonidine EC50 after either one or 21 injections. Only desmethylimipramine had a significant effect on noradrenaline responsiveness, producing an inconsistent decrease in EC50 with a consistent increase in maximum contractile response after 21 but not after one daily injection(s). Clorgyline (10(-5) M) increased the contractile response of the isolated vas deferens to field stimulation and antagonized the inhibitory effect of clonidine when added directly to the isolated tissue preparation. Neither clorgyline (5 mg kg-1), selegiline (1 mg kg-1) nor tranylcypromine (2.5 mg kg-1) affected significantly the inhibitory response to clonidine (1 microgram kg-1) on contractions of in situ sympathetically stimulated vas deferens in pithed rats. These results show that down-regulation of alpha 2-presynaptic adrenoceptors by chronic treatment with desmethylimipramine and clorgyline occurs in peripheral organs as well as in the central nervous system.
在给大鼠每日注射去甲丙咪嗪、氯吉兰、司来吉兰或反苯环丙胺一次或21天后，测定大鼠离体输精管对可乐定（抑制0.1Hz场刺激引起的收缩）和去甲肾上腺素（纵肌收缩）的反应。去甲丙咪嗪（10mg/kg）和氯吉兰（2mg/kg）在每日注射21次后而非1次后，增加了离体输精管中可乐定的半数有效浓度（EC50）。反苯环丙胺（5mg/kg）在注射1次和21次后均增加了可乐定的EC50，而司来吉兰（1mg/kg）在注射1次或21次后均未影响可乐定的EC50。只有去甲丙咪嗪对去甲肾上腺素反应性有显著影响，在每日注射21次后而非1次后，使EC50不一致地降低，最大收缩反应一致增加。氯吉兰（10(-5)M）增加了离体输精管对场刺激的收缩反应，并在直接加入离体组织制剂时拮抗了可乐定的抑制作用。氯吉兰（5mg/kg）、司来吉兰（1mg/kg）和反苯环丙胺（2.5mg/kg）均未显著影响去大脑大鼠原位交感神经刺激的输精管收缩对可乐定（1μg/kg）的抑制反应。这些结果表明，长期用去甲丙咪嗪和氯吉兰治疗导致的α2-突触前肾上腺素能受体下调在外周器官以及中枢神经系统中均会发生。
