Constantine J W, Weeks R A, McShane W K
Eur J Pharmacol. 1978 Jul 1;50(1):51-60. doi: 10.1016/0014-2999(78)90252-2.
In vagotomized, spinal-sectioned dogs, prazosin and phentolamine enhanced positive chronotropic responses to cardiac accelerator nerve stimulation. In additional dogs the inhibition by clonidine of heart rate response to continuous accelerator nerve stimulation (presynaptic effect), and the vasopressor effect of clonidine (post-synaptic effect), were antagonized by prazosin, phentolamine and yohimbine; cumulative doses for 50% antagonism of the cardiac chronotropic effect were 103, 50 and 13 microgram/kg i.v., respectively, and those for 50% antagonism of the vasopressor effect were 39, 38 and 3 microgram/kg i.v., respectively. On isolated rabbit pulmonary artery, prazosin antagonized electrically evoked contractions but had no effect on 3H output, whereas yohimbine enhanced both. The results indicate that prazosin, like phentolamine and yohimbine, blocks presynaptic alpha-adrenergic receptors on the cardiac accelerator nerve of the dog but, unlike yohimbine, prazosin does not block these receptors on noradrenergic nerves of rabbit pulmonary artery. It is concluded that the relative activity of a compound at pre- and postsynaptic alpha-receptors is not the same for all organs. The results are discussed relative to the fact that prazosin causes hypotension without significant reflex tachycardia in dog and man.
在迷走神经切断、脊髓横断的犬中，哌唑嗪和酚妥拉明增强了对心脏加速神经刺激的正性变时反应。在另外的犬中，可乐定对连续加速神经刺激的心率反应的抑制作用（突触前效应）以及可乐定的升压作用（突触后效应），被哌唑嗪、酚妥拉明和育亨宾所拮抗；使心脏变时效应50%被拮抗的累积剂量分别为静脉注射103、50和13微克/千克，使升压效应50%被拮抗的累积剂量分别为静脉注射39、38和3微克/千克。在离体兔肺动脉上，哌唑嗪拮抗电诱发的收缩，但对3H释放无影响，而育亨宾则增强两者。结果表明，哌唑嗪与酚妥拉明和育亨宾一样，阻断犬心脏加速神经上的突触前α-肾上腺素能受体，但与育亨宾不同的是，哌唑嗪不阻断兔肺动脉去甲肾上腺素能神经上的这些受体。得出的结论是，一种化合物在突触前和突触后α受体上的相对活性对所有器官来说并不相同。结合哌唑嗪在犬和人中引起低血压而无明显反射性心动过速这一事实对结果进行了讨论。
