Dubocovich M L, Langer S Z, Massingham R
Br J Pharmacol. 1980 May;69(1):81-90. doi: 10.1111/j.1476-5381.1980.tb10885.x.
1 LD 3098 (cirazoline) is an imidazoline derivative, possessing agonist properties at alpha-adrenoceptor sites.2 When transmitter release was measured directly as tritium overflow from perfused cat spleen preparations, prelabelled with [(3)H]-noradrenaline, LD 3098 was found to be 10 times more selective for presynaptic than for postsynaptic alpha-adrenoceptors.3 In addition, in this preparation, LD 3098 appears to induce a postsynaptic sensitization to the transmitter released by nerve depolarization because under conditions in which [(3)H]-noradrenaline overflow decreased, there was a paradoxical potentiation in the response to nerve stimulation. This potentiation also occurred with a concentration of LD 3098 that did not per se affect stimulation-evoked [(3)H]-noradrenaline release or the basal perfusion pressure of the spleen.4 Both the reduction in (3)H-transmitter release induced through activation of alpha-presynaptic adrenoceptors and the potentiation of the responses to nerve stimulation were concentration-dependent phenomena.5 In pentobarbitone anaesthetized dogs, the heart rate response to low frequency ansa-subclavia stimulation was not affected by LD 3098. Whilst the alpha(1) mediated increase in blood pressure responses to injected noradrenaline and tyramine was significantly potentiated by LD 3098, the beta(1)-mediated heart rate responses to these injected amines were not modified in the presence of LD 3098.6 Thus it is possible that the failure to detect any presynaptic effects with LD 3098 when transmitter release is measured indirectly at the level of the postsynaptic responses is due to end organ sensitivity changes.7 These findings emphasize that caution is necessary when assessing presynaptic alpha-adrenoceptor effects through end organ responses to nerve stimulation both in vitro and in vivo and the need for measurements of transmitter overflow as well as adequate postsynaptic controls in such experiments.
LD 3098（西拉唑啉）是一种咪唑啉衍生物，对α-肾上腺素能受体位点具有激动剂特性。
当以灌注猫脾脏制剂中[³H] - 去甲肾上腺素的氚溢出量直接测量递质释放时，发现LD 3098对突触前α-肾上腺素能受体的选择性比对突触后α-肾上腺素能受体高10倍。
此外，在该制剂中，LD 3098似乎会诱导对神经去极化释放的递质产生突触后敏感化，因为在[³H] - 去甲肾上腺素溢出减少的情况下，对神经刺激的反应出现了反常的增强。这种增强在LD 3098的浓度下也会发生，该浓度本身并不影响刺激诱发的[³H] - 去甲肾上腺素释放或脾脏的基础灌注压力。
通过激活突触前α-肾上腺素能受体诱导的³H-递质释放减少以及对神经刺激反应的增强都是浓度依赖性现象。
在戊巴比妥麻醉的狗中，LD 3098不影响对低频锁骨下袢刺激的心率反应。虽然LD 3098显著增强了α₁介导的对注射去甲肾上腺素和酪胺的血压反应增加，但在存在LD 3098的情况下，β₁介导的对这些注射胺类的心率反应没有改变。
因此，当在突触后反应水平间接测量递质释放时，未能检测到LD 3098的任何突触前效应可能是由于终末器官敏感性变化。
这些发现强调，在体外和体内通过终末器官对神经刺激的反应评估突触前α-肾上腺素能受体效应时，必须谨慎，并且在此类实验中需要测量递质溢出以及进行适当的突触后对照。
