Ozawa H, Uematsu T
Tohoku J Exp Med. 1976 Jul;119(3):283-91. doi: 10.1620/tjem.119.283.
The bradycardia-inducing effects of clonidine were examined in anesthetized or spinal rats by injecting the drug intracisternally (i.c.) or intravenously (i.v.). Clonidine (1-25mug i.c.) caused a bradycardia dose-dependently in anesthetized rats. The bradycardia in response to clonidine (5mug i.c.) was significantly reduced after a treatment with phentolamine (100 mug i.c.), but not influenced with atropine (1 mg i.v.) or sectioning bilateral cervical vagal nerves. In spinal rats, an acceleration in heart rate by electrical stimulation of cervical sympathetic nerves was frequency-dependent and that due to desmethylimipramine (DMI) was dose-dependent. Clonidine (30 mug i.v.) significantly inhibited the acceleration induced by electrical stimulations only at a low frequency (0.3-3 Hz) or DMI (0.3 mg i.v.). This inhibition by clonidine was antagonized by phentolamine (5 mg i.v.). Clonidine (30 mug i.v.) did not significantly influence the acceleration in heart rate of spinal rats induced by norepinephrine (1 mug i.v.), tyramine (100 mug i.v.) or 1,1-dimethyl-4-phenylpiperazinium (DMPP, 50 mug i.v.). Therefore, it is suggested that clonidine causes a bradycardia by stimulating both peripheral and central alpha-adrenoceptors, the sympathetic trunk is the main pathway, and that the peripheral mechanism for clonidine-induced bradycardia is different from the action of guanethidine or hexamethonium on a release of catecholamines from the cardiac nerve terminals.
通过脑池内（i.c.）或静脉内（i.v.）注射药物，在麻醉大鼠或脊髓大鼠中研究可乐定的致心动过缓作用。可乐定（1 - 25μg，i.c.）在麻醉大鼠中剂量依赖性地引起心动过缓。用酚妥拉明（100μg，i.c.）处理后，对可乐定（5μg，i.c.）的心动过缓反应显著降低，但不受阿托品（1mg，i.v.）或切断双侧颈迷走神经的影响。在脊髓大鼠中，电刺激颈交感神经引起的心率加快是频率依赖性的，而去甲丙咪嗪（DMI）引起的心率加快是剂量依赖性的。可乐定（30μg，i.v.）仅在低频（0.3 - 3Hz）电刺激或DMI（0.3mg，i.v.）时显著抑制心率加快。可乐定的这种抑制作用被酚妥拉明（5mg，i.v.）拮抗。可乐定（30μg，i.v.）对去甲肾上腺素（1μg，i.v.）、酪胺（100μg，i.v.）或1,1 - 二甲基 - 4 - 苯基哌嗪鎓（DMPP，50μg，i.v.）诱导的脊髓大鼠心率加快无显著影响。因此，提示可乐定通过刺激外周和中枢α - 肾上腺素能受体引起心动过缓，交感干是主要途径，且可乐定诱导心动过缓的外周机制不同于胍乙啶或六甲铵对心脏神经末梢儿茶酚胺释放的作用。
