Bradshaw C M, Stoker M J, Szabadi E
Naunyn Schmiedebergs Arch Pharmacol. 1982 Sep;320(3):230-4. doi: 10.1007/BF00510133.
The technique of microelectrophoresis was used in order to examine the effects of clonidine on single neurones in the somatosensory cortex of the rat, and to compare its actions with those of noradrenaline and phenylephrine. Clonidine evoked only excitatory responses on cortical neurones. The clonidine-sensitive neurones were also excited by noradrenaline and phenylephrine. Clonidine had a consistently lower apparent potency than either noradrenaline or phenylephrine. Responses to clonidine had a slower time-course than responses to the other two adrenoceptor agonists, both the latencies to onset and the recovery times being longer for responses to clonidine than for responses to noradrenaline and phenylephrine. When the mobilities of clonidine and phenylephrine were compared using an in vitro method, no significant difference was found between the mobilities of the two ionic species, suggesting that they have similar transport numbers. Thus the difference between the potencies and time-courses of responses to clonidine and phenylephrine are presumably of biological origin. Responses to clonidine were antagonised by microelectrophoretically applied prazosin; responses to phenylephrine were equally antagonised, while responses to acetylcholine were not affected. Clonidine could reversibly antagonise excitatory responses to both noradrenaline and phenylephrine, without affecting responses to acetylcholine. The results suggest that clonidine may act as a partial agonist at excitatory alpha 1-adrenoceptors on cortical neurones.
采用微电泳技术研究可乐定对大鼠体感皮层单个神经元的作用,并将其作用与去甲肾上腺素和苯肾上腺素进行比较。可乐定仅引起皮层神经元的兴奋反应。对可乐定敏感的神经元也可被去甲肾上腺素和苯肾上腺素兴奋。可乐定的表观效价始终低于去甲肾上腺素或苯肾上腺素。可乐定引起的反应时相比其他两种肾上腺素能受体激动剂更慢,可乐定反应的起效潜伏期和恢复时间均长于去甲肾上腺素和苯肾上腺素的反应。采用体外方法比较可乐定和苯肾上腺素的迁移率时,未发现两种离子型药物迁移率的显著差异,提示它们具有相似的迁移数。因此,可乐定和苯肾上腺素效价及反应时相的差异可能源于生物学因素。微电泳施加的哌唑嗪可拮抗可乐定引起的反应;苯肾上腺素引起的反应同样可被拮抗,而乙酰胆碱引起的反应不受影响。可乐定可可逆性拮抗去甲肾上腺素和苯肾上腺素的兴奋反应,而不影响乙酰胆碱引起的反应。结果提示,可乐定可能作为皮层神经元兴奋性α1-肾上腺素能受体的部分激动剂发挥作用。