Cavero I, Gomeni R, Lefèvre-Borg F, Roach A G
Br J Pharmacol. 1980 Feb;68(2):321-32. doi: 10.1111/j.1476-5381.1980.tb10421.x.
1 The cardiovascular effects of intravenous desipramine (0.03 and 0.1 mg/kg), maprotiline (0.5 mg/kg), mianserin (1.0 and 3.0 mg/kg) and phentolamine (0.25 mg/kg) were examined and compared in pithed rats. Several experimental procedures were used in order to distinguish between the effects of the compounds on cardiac presynaptic alpha-adrenoceptors and on neuronal noradrenaline reuptake, as inhibition of either mechanism produces an increase of neurotransmitter concentration within the sympathetic synapse and therefore results in a greater end organ response.2 Pressor responses elicited by noradrenaline were potentiated by desipramine and maprotiline, reduced by phentolamine and not significantly modified by mianserin. However, all four compounds inhibited the pressor action of tyramine. Furthermore, mianserin reduced the pressor response to adrenaline.3 Desipramine, maprotiline and mianserin, but not phentolamine enhanced the positive chronotropic effects of noradrenaline, without affecting those of isoprenaline.4 All four compounds abolished the clonidine-induced inhibition of heart rate responses to short term electrical stimulation of the spinal cord. Moreover, in rats with a persistent tachycardia (induced by continuous stimulation of the thoracic spinal cord) desipramine, maprotiline and mianserin further increased heart rate. This effect was also observed in animals pretreated with phentolamine, administered in order to inhibit cardiac presynaptic alpha-adrenoceptors.5 In rats with a sustained tachycardia (100 beats/min produced by electrical stimulation of the spinal cord) both mianserin and phentolamine, in contrast to desipramine, shifted the clonidine heart rate dose-response curve to the right. Phentolamine was about 34 times more potent than mianserin in this respect.6 In pithed, reserpine-treated rats, the pressor responses to clonidine were not significantly modified by desipramine. The dose-response curves were shifted to the right by phentolamine (0.25 mg/kg) and mianserin (3.0 mg/kg).7 These results indicate that mianserin is an antagonist of both cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors and also inhibits the neuronal reuptake of noradrenaline.
在脊髓被切断的大鼠中，研究并比较了静脉注射去甲丙咪嗪（0.03和0.1毫克/千克）、马普替林（0.5毫克/千克）、米安色林（1.0和3.0毫克/千克）和酚妥拉明（0.25毫克/千克）对心血管系统的影响。采用了几种实验方法，以区分这些化合物对心脏突触前α-肾上腺素能受体和神经元去甲肾上腺素再摄取的影响，因为抑制这两种机制中的任何一种都会导致交感神经突触内神经递质浓度增加，从而导致终末器官反应增强。
去甲丙咪嗪和马普替林增强了去甲肾上腺素引起的升压反应，酚妥拉明减弱了该反应，而米安色林则无显著影响。然而，所有四种化合物均抑制了酪胺的升压作用。此外，米安色林降低了对肾上腺素的升压反应。
去甲丙咪嗪、马普替林和米安色林增强了去甲肾上腺素的正性变时作用，但不影响异丙肾上腺素的正性变时作用，而酚妥拉明无此作用。
所有四种化合物均消除了可乐定对脊髓短期电刺激引起的心率反应的抑制作用。此外，在持续性心动过速（由胸段脊髓持续刺激诱导）的大鼠中，去甲丙咪嗪、马普替林和米安色林进一步增加了心率。在用酚妥拉明预处理以抑制心脏突触前α-肾上腺素能受体的动物中也观察到了这种效应。
在持续性心动过速（由脊髓电刺激产生100次/分钟）的大鼠中，与去甲丙咪嗪相反，米安色林和酚妥拉明均使可乐定心率剂量反应曲线右移。在这方面，酚妥拉明的效力比米安色林强约34倍。
在脊髓被切断、经利血平处理的大鼠中，去甲丙咪嗪对可乐定的升压反应无显著影响。酚妥拉明（0.25毫克/千克）和米安色林（3.0毫克/千克）使剂量反应曲线右移。
这些结果表明，米安色林是心脏突触前和血管突触后α-肾上腺素能受体的拮抗剂，并且还抑制去甲肾上腺素的神经元再摄取。
